1.Protective effect of Addie in treatment of cardiac injury induced by radiotherapy and chemotherapy in patients with cervical cancer
Chinese Journal of Biochemical Pharmaceutics 2017;37(2):116-119
Objective To investigate the protective effect of Addie on cardiac injury induced by radiotherapy and chemotherapy in patients with cervical cancer.Methods 74 cases of cervical cancer were collected from the oncology department of Zhousha Hospital, those were treated with surgery and radiotherapy and chemotherapy according to postoperative staging and classification of cases.The patients were randomly divided into the experimental group and the control group, with 37 cases in each group.Control group received leukogenic and antiemetic treatment,the experimental group were given Addie injection 100 mL intravenous drip on the basis of the control group, one times per day,10 days as one courses, and two groups were all received 6 courses of treatment.Atthe end of treatment, the condition of heart function, left ventricular ejection fraction, left ventricular end diastolic diameter, 6 minutes walk test, myocardial enzymes, troponin T, C reactive protein /Barhel quality of life score index, EORTC-QLQ score and the incidence of adverse reactions were detected and compared with two groups.Results After treatment, the cardiac function of the experimental group was significantly better than that of the control group (P<0.05).After treatment,LVEDD of two groups decreased (P<0.05), LVEF, 6 minutes walk test distance increased (P<0.05),and LVEDD of experimental group was lower than control group (P<0.05), LVEF, 6 minutes walk test distance higher (P<0.05).After treatment, creatine kinase and creatine kinase levels were increased in two groups (P<0.05).Compared with the control group, the level of creatine kinase and creatine kinase in experimental group were higher(P <0.05).After treatment,the levels of troponin T and C reactive protein in two groups were decreased ( P <0.05 ) .Compared with the control group, the levels of troponin T and C reactive protein in experimental group were lower (P<0.05).After treatment,the scores of Barhel index and EORTC-QLQ score of two groups were significantly higher than before treatment, and the quality of life of the experimental group was significantly higher than that of control group ( P <0.05 ) .There was no significant difference in the incidence of adverse reactions between two groups.Conclusion Addie has an obvious protective effect on cardiac injury induced by radiotherapy and chemotherapy in patients with cervical cancer, and can improve the quality of life of patients.
2.Application of activatable cell-penetrating peptide in the field of tumor therapy.
Li ZHANG ; Gang WEI ; Weiyue LU
Acta Pharmaceutica Sinica 2014;49(12):1639-43
Cell-penetrating peptide (CPP) is a kind of small molecular peptide which can pass through a variety of cell membranes. It can carry bioactive macromolecules into cells. Due to lacking of tissue-selecting and targeting behavior, the application of CPP in the field of tumor treatment is limited. Activatable cell- penetrating peptide (ACPP) has brought the dawn to the application of CPP. This review mainly introduces the applications of ACPP in the targeting antitumor drug delivery which was designed based on the differences between tumor microenvironment and normal tissues as well as the exogenous physical stimulation.
3.Protective effect of Shen Mai injection in the treatment of lung injury induced by radiotherapy in patients with advanced breast cancer
Weiyue HE ; Qilun LU ; Changjing HUANG
Chinese Journal of Biochemical Pharmaceutics 2017;37(1):94-96,100
Objective To investigate the protective effect of Shen Mai injection in the treatment of lung injury induced by radiotherapy in patients with advanced breast cancer. Methods 80 cases with lung injury induced by radiotherapy in patients with advanced breast cancer from our hospital from 2015.1 to 2016.5 were selected and randomly divided into 2 groups, 40 cases in control group were given routine treatment, 40 cases in the experimental group were treated based on the control group treated with Shenmai injection treatment, and 2 groups were treated for 4 weeks. The pulmonary function, T lymphocyte subsets, clinical symptoms, quality of life scores and clinical efficacy were observed before and after treatment in two groups. The results were analyzed by statistical software SPSS 19.0. Results Compared with before treatment, levels of FVC, FEV1 and TLC in 2 groups after treatment elevated, scores of respiratory symptoms, activities, and daily life effect decreased, levels of serum CD3+, CD4+, CD4+/CD8+elevated, levels of CD8+ decreased, and compared with the control group, levels of FVC, FEV1, TLC, CD3+, CD4+, CD4+/CD8+ in the experimental group were higher, scores of respiratory symptoms, activities, and daily life effect were lower, clinical effect rate was higher, the differences were statistically significant (P<0.05). Conclusion Shen Mai injection can effectively improve lung function and immunity, improve respiratory symptoms and improve the quality of life in patients with advanced breast cancer radiotherapy for lung injury, and has better clinical efficacy.
4.Preparation and in vitro targeting of sterically stabilized liposomes modified with chimeric TNT-3 monoclonal antibody
Hong PAN ; Guoqin NIU ; Jun PAN ; Weiyue LU
Acta Pharmaceutica Sinica 2006;41(6):506-512
Aim To prepare sterically stabilized liposomes modified with chimeric TNT-3 monoclonal antibody (chTNT-3) and investigate their immunoreactivity and in vitro targeting. Methods An endgroup functionalized polyethylene glycol-lipid derivative (pyridylthiopropionoylamino-polyethylene glycolhydrogenated soy phosphatidylethanolamine, PDP-PEG-HSPE ) was synthesized and incorporated to sterically stabilized liposomes. After mild thiolysis of the PDP groups by dithiothreitol, liposomes were covalently linked with maleimide-derivatized chTNT-3 and formed sterically stabilized immunoliposomes.Coupling efficiency, antibody density, size distribution, immunoreactivity of chTNT-3-modified sterically stabilized liposomes (chTNT-3-SLs) and specific binding properties of the chTNT-3-SLs to fixed Raji cells were determined, separately. Results Higher initial Ab/PDP-PEG-HSPE molar ratios resulted in higher antibody density on the surface of liposomes but lower coupling efficiency. The optimal coupling efficiency of 71% was obtained while antibody density in liposome was 106 μg antibody/μmol phospholipids (as initial antibody/PDP-PEG-HSPE = 1: 10). The chTNT-3-SLs had a narrow size distribution after extrusion and the mean size of this immunoliposomes was (115 ± 33) nm. The immunoreactivity of chTNT-3 can be preserved after efficient attachment of maleimide-derivatized chTNT-3 to the surface of liposomes. But calculated per antibody concentration, the immunoreactivity of chTNT-3-SLs would obviously decrease compared to that of chTNT-3 or chTNT-3 derivatives. Significantly higher binding of chTNT-3-SLs to fixed Raji cells directed by chTNT-3 was obtained compared to other preparations in serial dilutions (P<0.01). Conclusion chTNT-3-SLs prepared by PDP-PEG-HSPE method remained most immunoreactivity of chTNT-3 and was able to bind nuclear antigens in vitro.
5.Preparation of bovine serum albumin nanoparticles loaded with gemcitabine and the cytotoxic effect on pancreatic cancer cells in vitro
Jinming LI ; Wei CHEN ; Jiang LONG ; Chen JIN ; Weiyue LU ; Quanxing NI ; Deliang FU ; Huimin HOU
Chinese Journal of Pancreatology 2008;8(5):295-297
Objectives To investigate preparation of gemcitabine albumin nanoparticles, and its property of slow-release, the cytotoxic effect on pancreatic cancer cells (PANC1) in vitro, for improving the effect of regional intra-arterial infusion chemotherapy in pancreatic cancer with new medicament in the future. Methods The gemcitabine albumin nanoparticles were prepared with bovine serum albumin and gemcitabine with the desolvation-crosslink method, the concentration of gemcitabine was detected by high performance liquid chromatography (HPLC). The cytotoxic effect on pancreatic cancer cells in vitro were detected with MTT colorimetric assay. Results The mean diameter of gemcitabine albumin nanoparticles was (156.2±2.2) nm, and Zeta potential was (-20.4±1.41)mV, drug loading was 10.8%, drug release time in virto was 3 hours respectively. Gemcitabine albumin nanoparticles (0.01~50 μg/ml) had a 31%~44% inhibitory rate on PANC1 cell, which was similar to the inhibitory rate of same concentration of gemcitabine (26%~47%). Conclusions The new preparation of gemcitabine albumin nanoparticles had obvious drug slow-release effect, which may help improve the effect of regional intra-arterial infusion chemotherapy for pancreatic cancer.
6.Modification by wheat germ agglutinin delays the ocular elimination of liposome.
Wenjian ZHANG ; Dongxiao YANG ; Linglin FENG ; Fei WANG ; Gang WEI ; Weiyue LU
Acta Pharmaceutica Sinica 2014;49(4):543-9
The purpose of this study is to explore the feasibility of wheat germ agglutinin (WGA) modified liposome as a vehicle for ophthalmic administration. Liposome loaded with 5-carboxyfluorescein (FAM) was prepared by lipid film hydration method. WGA was thiolated and then conjugated to the surface of the liposome via polyethylene glycol linker to constitute the WGA-modified and FAM-loaded liposome (WGA-LS/FAM). The amount of thiol groups on each WGA molecule was determined, and the bioactivity of WGA was estimated after it was modified to the surface of liposome. The physical and chemical features of the WGA-modified liposome were characterized and the ocular bioadhesive performance was evaluated in rats. The result showed that each thiolated WGA molecule was conjugated with 1.32 thiol groups. WGA-LS/FAM had a mean size of (97.40 +/- 1.39) nm, with a polydispersity index of 0.23 +/- 0.01. The entrapment efficacy of FAM was about (2.95 +/- 0.21)%, and only 4% of FAM leaked out of the liposome in 24 h. Erythrocyte agglutination test indicated that after modification WGA preserved the binding activity to glycoprotein. The in vivo ocular elimination of WGA-LS/FAM fitted first-order kinetics, and the elimination rate was significantly slower than that of the unmodified liposome, demonstrating WGA-modified liposome is bioadhesive and suitable for ophthalmic administration.
7.Targeting therapy of magnetic doxorubicin stealth liposome on human gastric cancer xenografts in nude mice
Yishu LIU ; Liqing YAO ; Pinghong ZHOU ; Xizhong SHEN ; Weiyue LU ; Ming YAO ; Zhijiang WU ; Yajun SUN
Chinese Journal of General Surgery 1993;0(03):-
Objective To study the effect of magnetic doxorubicin stealth liposome on human gastric cancer xenografts in nude mice.Methods Human gastric cancer cell line MKN-45 was implanted into 36 nude mice.Different kinds of drug were injected through the caudal vein of tumor bearing nude mice divided into 6 groups .Permanent magnet was put into tumor in targeting group.Results The growth speed of tumor in the group of MDL (+) significantaly slowed down than other groups.The rate of tumor restrain in tumor weight and tumor volume of MDL (+) group were 71% and 70%, which were remarkably higher than those of the DOX and MDL (-) group (all P
8.Enhanced glioma-targeting and stability of GICP peptide coupled with stabilized peptide A7R.
Acta Pharmaceutica Sinica B 2018;8(1):106-115
Malignant glioma is usually accompanied by vigorous angiogenesis to provide essential nutrients. An effective glioma targeting moiety should include excellent tumor-cell homing ability as well as good neovasculature-targeting efficiency, and should be highly resistant to enzyme degradation in the bloodstream. The phage display-selected heptapeptide, the glioma-initiating cell peptide (GICP), was previously reported as a ligand for the VAV3 protein (a Rho-GTPase guanine nucleotide exchange factor), which is mainly expressed on glioma cells; the stabilized heptapeptide A7R has been shown to be the ligand of both vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1), and has demonstrated good neovasculature-targeting ability. By linking A7R and GICP, a multi-receptor targeting molecule was obtained. The stability of these three peptides was evaluated and their targeting efficiency on tumor-related cells and models was compared. The ability of these peptides to cross the blood--tumor barrier (BTB) was also determined. The results indicate that the coupled Y-shaped peptide A7R-GICP exhibited improved tumor and neovasculature targeting ability and had higher efficiency in crossing the BTB than either individual peptide.
9.Computation of relative biological effectiveness of low-energy electrons release in gadolinium neutron capture therapy based on microdosimetry
Weiyue YU ; Bing HONG ; Peng LU ; Lizhen LIANG ; Ni CHEN
Chinese Journal of Radiological Medicine and Protection 2023;43(5):373-378
Objective:To calculate the relative biological effectiveness (RBE) value of the released low-energy electrons in gadolinium neutron capture therapy ( 157GdNCT) based on microdosimetry. Methods:The Monte Carlo (MC) code Geant4-DNA package was used to simulate the energy deposition distribution and microdosimetry parameters of low-energy electrons released during gadolinium neutron capture treatment in different sensitive target volumes and physical models on track structures. On this basis, RBE value was obtained based on the microdosimetry kinetic model (MKM).Results:The low-energy electron RBE value was highly variable in different sensitive target volumes and decreases with increasing sensitive target volumes. With 6-nm-diameter sensitive target as reference, RBE value was 1.77 for 6-nm diameter, 1.53 for 10 nm diameter with percentage difference 13%, and 1.40 for 15-nm diameter with percentage difference of 21%, respectively. The effect of different Geant4-DNA physical models on the RBE of low-energy electrons was small. Using the RBE value of 1.53 for physical model option2 as reference, the RBE values of option6 and option7 were 1.49 and 1.52, respectively, with the percentage differences of 2.6% and 0.6%, respectively.Conclusions:The RBE values of low energy electrons released by 157GdNCT in different sensitive target volumes and physical models were calculated by MKM to be 1.40-1.77.
10.Brain tumor-targeted drug delivery strategies.
Xiaoli WEI ; Xishan CHEN ; Man YING ; Weiyue LU
Acta Pharmaceutica Sinica B 2014;4(3):193-201
Despite the application of aggressive surgery, radiotherapy and chemotherapy in clinics, brain tumors are still a difficult health challenge due to their fast development and poor prognosis. Brain tumor-targeted drug delivery systems, which increase drug accumulation in the tumor region and reduce toxicity in normal brain and peripheral tissue, are a promising new approach to brain tumor treatments. Since brain tumors exhibit many distinctive characteristics relative to tumors growing in peripheral tissues, potential targets based on continuously changing vascular characteristics and the microenvironment can be utilized to facilitate effective brain tumor-targeted drug delivery. In this review, we briefly describe the physiological characteristics of brain tumors, including blood-brain/brain tumor barriers, the tumor microenvironment, and tumor stem cells. We also review targeted delivery strategies and introduce a systematic targeted drug delivery strategy to overcome the challenges.