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.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
4.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.
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.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.
7.Psoralen reverses glutathione-S-transferaseπ-mediated multidrug resistance in breast cancer stem cells
Yitong HUA ; Xiaohong WANG ; Chengfeng XU ; Kai CHENG ; Hongguang SUN ; Yingzhe ZHANG ; Jian LIU ; Zhenlin YANG
Chinese Journal of Tissue Engineering Research 2017;21(13):2003-2008
BACKGROUND:Breast cancer stem cells not only lead to theoccurrence of breast cancer, but also may cause breast cancer metastasis and recurrence. The relationship between stem cells and cell resistance is also gaining increasing attentions, and the focus on the stem cell treatment may result in unexpected results.OBJECTIVE:To explore the reversal effect of psoralen on glutathione-S-transferase π (GST-π) in human breast cancer MCF-7/ADR cells and its mechanism.METHODS:MCF-7/ADR cells were cultured and enriched in serum-free medium to obtain breast cancer stem cells.RT-PCR and western blot were used to detect the expression of GST-π at the levels of gene and protein in the MCF-7/ADR cells after treatment with 0, 4, 8, 12, 16 mg/L psoralen. To observe the activation of nuclear factor-κB,western blot was used. The expression of GST-π was detected by RT-PCR in 18 μmol/L SN50 group and 8 mg/L psoralen group. Cell counting kit-8 assay was used to detect the effect of doxorubicin on cell proliferation.RESULTS AND CONCLUSION:Compared with the control group, psoralen reduced the expression of GST-π at the mRNA and protein levels, and significantly inhibited the activation of nuclear factor-κB. It was suggested that psoralen could reverse the multidrug resistance of human breast cancer MCF-7/ADR stem cells by decreasing the expression level of GST-π. The mechanism may be achieved by inhibiting the nuclear factor-κB signal pathway.
8.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.
9.Comparative Study of the Effects of Application at Different Acupoints on the Quality of Life in Allergic Rhinitis Patients Based on Treating
yang Zheng ZHU ; ming Kai QI ; hua Li XUAN
Shanghai Journal of Acupuncture and Moxibustion 2017;36(12):1396-1400
Objective To observe the effects of application at different acupoints in improving the quality of life in allergic rhinitis patients. Method Seventy-seven patients with allergic rhinitis were randomized into a 12-point application group (39 cases) and a 6-point application group (38 cases), to receive Dong Bing Xia Zhi (treating cold-induced diseases in summer) application during each of the three periods of canicular days at corresponding points, 2 h each time. Rhinitis Quality of Life Questionnaire (RQLQ) was evaluated before and after the treatment, and half a year later. Result After the treatment, the total effective rate was 92.3% in the 12-point application group versus 71.1% in the 6-point application group, and the 12-point application group was significantly better (P<0.05); half a year later, the total effective rate was 87.2% in the 12-point application group versus 63.2% in the 6-point application group, and the 12-point group was significantly better (P<0.05); regarding the RQLQ, the 6-point application group didn't gain marked improvement in sleep quality after the treatment and half a year later (P>0.05), but the 12-point application group showed marked improvement (P<0.05); the rest component scores in RQLQ were significantly improved after the treatment and half a year later compared to those before the treatment in both groups (P<0.05); after the treatment, the 12-point application group was superior to the 6-point application group in comparing the reductionof all component scores and general score except the non-nose/eye symptoms score (P<0.05); half a year later, except the non-nose/eye symptoms and behavior scores, the 12-point application group was superior to the 6-point application group in comparing the reduction of all component scores and general score (P<0.05). Conclusion Dong Bing Xia Zhi acupoint application can effectively improve the quality of life in allergic rhinitis patients, especially with acupoints selected based on holism.
10.Relation between drug release and the drug status within curcumin-loaded microsphere.
De CHEN ; Yi LIU ; Kai-yan FAN ; Yi-qiao XIE ; An-an YU ; Zi-hua XIA ; Fan YANG
Acta Pharmaceutica Sinica 2016;51(1):140-146
To study the relation between drug release and the drug status within curcumin-loaded microsphere, SPG (shirasu porous glass) membrane emulsification was used to prepare the curcumin-PLGA (polylactic-co-glycolic acid) microspheres with three levels of drug loading respectively, and the in vitro release was studied with high-performance liquid chromatography (HPLC). The morphology of microspheres was observed with scanning electron microscopy (SEM), and the drug status was studied with X-ray diffraction (XRD), differential scanning calorimetry (DSC) and infrared analysis (IR). The drug loading of microspheres was (5.85 ± 0.21)%, (11.71 ± 0.39)%, (15.41 ± 0.40)%, respectively. No chemical connection was found between curcumin and PLGA. According to the results of XRD, curcumin dispersed in PLGA as amorphous form within the microspheres of the lowest drug loading, while (2.12 ± 0.64)% and (5.66 ± 0.07)% curcumin crystals was detected in the other two kinds of microspheres, respectively, indicating that the drug status was different within three kinds of microspheres. In the data analysis, we found that PLGA had a limited capacity of dissolving curcumin. When the drug loading exceeded the limit, the excess curcumin would exist in the form of crystals in microspheres independently. Meanwhile, this factor contributes to the difference in drug release behavior of the three groups of microspheres.
Calorimetry, Differential Scanning
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Curcumin
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chemistry
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Drug Liberation
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Lactic Acid
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Microscopy, Electron, Scanning
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Microspheres
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Polyglycolic Acid
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X-Ray Diffraction