1.The regulatory role of autophagy in tumor process.
Acta Pharmaceutica Sinica 2016;51(1):23-28
Autophagy is a classical regulatory mechanism of energy metabolism and self-update system in the maintenance of the intracellular homeostasis and cell development. Autophagy has been recently found to play a role in tumor development. Autophagy regulates tumor formation, proliferation, metastasis, and metabolism. At the same time, the anticancer drugs formed with autophagic mediators have been used in the treatment, which suggested that improving autophagy activity to inhibit tumor has become a new way for cancer treatment of cancer patients. This article gives an overview of the regulatory mechanism of autophagy, the relationship between autophagy and tumor, and tumor therapy by targeting autophagy.
Antineoplastic Agents
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Autophagy
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Humans
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Neoplasms
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physiopathology
2.The TGF-β signaling pathway induced EMT in breast cancer.
Yan MA ; Hong LIU ; Hao ZHANG ; Rong-guang SHAO
Acta Pharmaceutica Sinica 2015;50(4):385-392
Epithelial-mesenchymal transition (EMT) refers to tne transition during which epithelial cells undergo the loss of apical-basal polarity, acquisition of migration capability and transformation into mesenchymal cells. EMT induces breast cancer in situ to developing into metastasis and associates with the drug resistence. The multiple elements including signal pathways, transcriptional factors and downstream genes orchestrate the transition. Among them, the transforming growth factor β (TGF-β) signaling pathway plays a key role in the regulation of EMT in breast cancer. And this paper reviews the development of TGF-β signaling pathway induced EMT in breast cancer.
Breast Neoplasms
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metabolism
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Epithelial Cells
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Epithelial-Mesenchymal Transition
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Humans
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Signal Transduction
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Transcription Factors
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Transforming Growth Factor beta
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physiology
3.Improvement of dysphagia in patients with esophagus stenosis following carcinoma of esophagus
Ming LI ; Shao guang GAN ; Shizhou HUAN ; Rong fan CHEN ;
Chinese Journal of Tissue Engineering Research 2002;6(2):302-
Objective To investigate the intervention ways of endoscopes in the treatment of esophagus stenosis due to carcinoma of esophagus and improvement of quality. Method 11 cases of advanced carcinoma of esophagus were included in this study. Operation and chemical therapy were unavailable for these patients. Memory trestle with membrane and made of alloy of Nickel- titanium was inserted under intervention of endoscope. Trestle was posed in stenosis part of esophagus under direction of X- ray. Trestle could be dilated 3- 7 days after operation due to its reaction characteristics to temperature. So, redilated therapy was unnecessary. Trestle could reconstruct swallowing tract and made feeding through mouth become available during limited survival time.Results All trestles were successfully inserted.Half- fluid feeding was available after operation. Obstruction was removed in all patients(100% ).Conclusion Method described in this study was safe and effective .Effective swallowing tracts were reconstructed in all patients after trestle was planted and quality of life and survival time were both improved.
4.Establishment and application of a high-throughput drug screening model based on COL1A1 promoter for anti-liver fibrosis.
Shuang-Shuang ZHAO ; Ju-Xian WANG ; Yu-Cheng WANG ; Rong-Guang SHAO ; Hong-Wei HE
Acta Pharmaceutica Sinica 2015;50(2):169-173
For screening the potential drugs as anti-liver fibrosis candidates, we established a high- throughput drug screening cell model based on COL1A1 promoter. The activity of COL1A1 promoter and luciferase reporter gene can be elevated by TGF-β1, and inhibited by candidate drugs. We constructed a recombined plasmid with COL1A1 promoter and luciferase reporter gene pGL4.17, the activity of COL1A1 promoter was reflected by fluorescence intensity. COL1A1 promoter activity was detected by Dual-Luciferase Reporter Assay System, it came that the relative luciferase activity of COL1A1 promoter was 15.98 times higher than that of control group induced by TGF-β1, showing the recombined plasmid could be used in cell model. The recombined plasmid was transfected into human hepatic stellate cells LX2, detected the effect of potential drugs, and obtained a stable expression system through stable transfection and monoclonal cell culture. A sample which could reduce COL1A1 promoter activity signally by our cell model, decreased collagen I mRNA and protein expression detected by real-time RT-PCR and Western blotting. It indicates this novel cell model can be used in high-throughput drug screening of potential anti-liver fibrosis drugs.
Collagen Type I
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genetics
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Drug Evaluation, Preclinical
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methods
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Genes, Reporter
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Hepatic Stellate Cells
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High-Throughput Screening Assays
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Humans
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Liver Cirrhosis
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drug therapy
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Luciferases
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Plasmids
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Promoter Regions, Genetic
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RNA, Messenger
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Transfection
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Transforming Growth Factor beta1
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pharmacology
5.Significance of Computed Tomography in Diagnosis of Bronchial Foreign Body in Children
yan, SUN ; shao-hua, WANG ; rong-jun, LIN ; guang-feng, JIANG ; ying, TIAN ; zhi-jun, CHEN
Journal of Applied Clinical Pediatrics 2006;0(16):-
Objective To investigate clinical significance of computed tomography (CT) scan in diagnosis of bronchial foreign body in children.Methods Twenty-one suspected children with bronchial foreign body were studied with spiral CT cross-section scan and coronal reconstruction and diagnosis was confirmed with bronchoscopy.Results The foreign body was displayed in all of 21 cases. CT scan showed foreign body was located in right main bronchial 12 cases, right middle bronchial 1 case, right inferior lobar bronchial 2 cases and left main bronchial 6 cases. Foreign bodies were extracted with bronchoscopy.Conclusion CT scan can display and locate accurately foreign body in bronchial of children,and has very important diagnostic value in patients having atypical histories, clinical and radiological findings.
6.Inhibitions of SphK1 inhibitor SKI II on cell cycle progression and cell invasion of hepatoma HepG2 cells.
Cai-Xia ZHANG ; Hong LIU ; Yu-Yan GONG ; Hong-Wei HE ; Rong-Guang SHAO
Acta Pharmaceutica Sinica 2014;49(2):204-208
Sphingosine kinase 1 (SphK1) plays critical roles in cell biological functions. Here we investigated the effects of SphK1 inhibitor SKI II on hepatoma HepG2 cell cycle progression and invasion. Cell survival was determined by SRB assay, cell cycle progression was assayed by flow cytometry, the ability of cell invasion was measured by Matrigel-Transwell assay and protein expression was detected by Western blotting. The results showed that SKI II markedly inhibited HepG2 cell survival in a dose-dependent manner, induced G1 phase arrest in HepG2 cell and inhibited cell invasion. SKI II markedly decreased the expressions of G1-phase-related proteins CDK2, CDK4 and Cdc2 and the levels of cell invasion-associated proteins MMP2 and MMP9. The results showed that SKI II inhibited cell cycle progression and cell invasion, implying SphK1 as a potential target for hepatoma treatment.
CDC2 Protein Kinase
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Cell Movement
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drug effects
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Cell Survival
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drug effects
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Cyclin-Dependent Kinase 2
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metabolism
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Cyclin-Dependent Kinase 4
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metabolism
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Cyclin-Dependent Kinases
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metabolism
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G1 Phase
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drug effects
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Hep G2 Cells
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Humans
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Matrix Metalloproteinase 2
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metabolism
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Matrix Metalloproteinase 9
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metabolism
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Phosphotransferases (Alcohol Group Acceptor)
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antagonists & inhibitors
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Thiazoles
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pharmacology
7.The synergistic effect of lidamycin and rituximab on human B cell lymphoma.
Yi-Ran SUN ; Sheng-Hua ZHANG ; Rong-Guang SHAO ; Hong-Wei HE
Acta Pharmaceutica Sinica 2014;49(2):198-203
This study aimed to investigate the synergistic effect of lidamycin (LDM) and rituximab on human B cell lymphoma Ramos cells. Cell proliferation was measured using MTS assay, cell apoptosis was analyzed by Annexin V-FITC/PI assay, the expression of apoptosis related proteins was analyzed by Western blotting, and the in vivo lymphoma inhibition was verified using BALB/c mice inoculated via tail vein using Ramos cells which stably expressed pEGFP-N1 plasmid. The results showed that, after the pretreatment with rituximab for 48 h, rituximab and LDM showed significantly synergistic effects on cell proliferation. Cells in combined treatment group had a higher apoptosis rate than that in LDM treatment group. Compared with the LDM treatment group, the expression of apoptosis-related proteins such as Cleaved caspase-3, Cleaved caspase-7, Cleaved caspase-9 and Cleaved PARP in combined treatment groups increased, and expression of cIAP-2 and Bcl-2 decreased. The result of in vivo experiment showed that, in the combined treatment group, the survival time of BALB/c mice was significantly longer than the mice in control group and LDM treatment group, and the degree of tumor accumulation and metastasis to lymph nodes and spleen was lower.
Aminoglycosides
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pharmacology
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Animals
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Antibiotics, Antineoplastic
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pharmacology
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Antineoplastic Agents
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pharmacology
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Apoptosis
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drug effects
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Caspase 3
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metabolism
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Caspase 7
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metabolism
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Caspase 9
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metabolism
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Cell Line, Tumor
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Cell Proliferation
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drug effects
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Drug Synergism
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Enediynes
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pharmacology
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Humans
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Inhibitor of Apoptosis Proteins
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metabolism
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Lymphoma, B-Cell
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metabolism
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pathology
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Neoplasm Metastasis
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Neoplasm Transplantation
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Poly(ADP-ribose) Polymerases
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metabolism
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Proto-Oncogene Proteins c-bcl-2
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metabolism
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Random Allocation
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Rituximab
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pharmacology
8.An overview of antibody-based cancer therapy.
Qing-fang MIAO ; Rong-guang SHAO ; Yong-su ZHEN
Acta Pharmaceutica Sinica 2012;47(10):1261-1268
The use of monoclonal antibodies (mAbs) for cancer therapy has achieved considerable success in recent years. Approximate 17 monoclonal antibodies have been approved as cancer therapeutics since 1997. Antibody-drug conjugates (ADC) are powerful new treatment options for cancer, and naked antibodies have recently achieved remarkable success. The safety and effectiveness of therapeutic mAbs in oncology vary depending on the nature of the target antigen and the mechanisms of tumor cell killing. This review provides a summary of the current state of antibody-based cancer therapy, including the mechanisms of tumor cell killing by antibodies, tumor antigens as antibody targets, clinical effectiveness of antibodies in cancer patients and nanoparticles-based ADCs.
Antibodies, Monoclonal
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immunology
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therapeutic use
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Antigens, Neoplasm
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immunology
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Antineoplastic Agents
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therapeutic use
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Humans
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Immunoconjugates
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therapeutic use
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Nanoparticles
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Neoplasms
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immunology
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therapy
9.Small interfering RNA mediated multi-target therapy of cancer.
Acta Pharmaceutica Sinica 2009;44(3):219-225
It has been reviewed that as many as hundreds genes are dysregulated in various kinds of cancers, yet most therapies are targeted toward a single gene. Recently, the mode of cancer treatment has been changed by a shift in thinking from mono-target to multi-target therapies. There is considerable evidence that these have a higher possibility of success than mono-target therapy, and multi-target therapy should remain the most attractive avenue for future treatment strategies. In this article, we attempt to provide evidence for the role of small interfering RNA in multi-target therapy of cancer.
Animals
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Genetic Therapy
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Humans
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Neoplasms
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genetics
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therapy
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RNA Interference
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RNA, Small Interfering
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genetics
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therapeutic use
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Radiation Tolerance
10.Comparison of the effect of positive and negative oral contrast agents on delineation and 18F-FDG uptake of gastrointestinal tract
De-gang, MENG ; Xiao-guang, SUN ; Gang, HUANG ; Jian-jun, LIU ; Shao-li, SONG ; Liang-rong, WAN
Chinese Journal of Nuclear Medicine 2010;30(4):272-275
Objective To compare the different effects of 1% diatrizoate meglumine,2.5% mannitol and water as oral contrasts in PET/CT scan in gastrointestinal tract delineation and 18F-fluorodeoxyglucose (FDG) uptake. Methods Sixty-one patients referred for PET/CT scan without gastrointestinal diseases were divided into three groups randomly ( random number method). One liter of 1% diatrizoate meglumine,2.5% mannitol,or water was orally taken by groups 1 (25 cases),2 (20 cases) and 3 ( 16 cases),respectively before scan. The scan was performed with GE Discovery LS PET/CT scanner in two-dimensional (2D) mode 50 min after 18F-FDG (5.55 MBq/kg) injection. Patients with abdominal lesions were excluded from this study. The degree of gastrointestinal filling and 18F-FDG uptake was evaluated by 3 nuclear medicine physicians using visual analysis according to a 4-grade classification method:none,mild,moderate,and high. Statistically analysis was performed by Kruskal-Wallis,Mann-Whitney and paired t tests.Results Both the differences of serum glucose and insulin levels were not significant before and after contrast taken in group 2. Group 2 had better gastrointestinal filling than that of group 1 and also better than group 3 except in rectum. The stomach,jejunum,ascending,and transverse colon were better filled in group 1 than in group 3. The degree of 18F-FDG uptake of group 3 was significantly higher than that of group 2 in stomach,jejunum and ileum (z= -3. 192,-3.290,-3.290,all P<0.05),and was also significantly higher than that of group 1 (z = - 3. 603,P < 0.05) in jejunum. The degree of 18 F-FDG uptake of group 3 was significantly lower than that of group 1 in ascending colon (z = - 2. 706,P < 0. 05 ) and was significantly lower than that of group 1 and 2 in transverse and descending colon (z= - 3. 503,- 2.403,- 4.225,-4. 027,all P <0.05),and was also significantly lower than that of group 2 in rectum (z = -4. 128,P <0. 01 ). The maximum CT values in stomach,jejunum,ileum and ascending colon in group 1 were ( 132 ±23),(191 ±31),(313 ±47) and (374±53) HU,respectively,whose difference was significant (t = -7.088--1.781,all P <0. 01 ). Conclusion Oral iso-osmotic mannitol intake has better gastrointestinal filling and less physiological 18F-FDG uptake compared to diatrizoate meglumine and water.