Molecular target-based cancer therapy is playing a more and more important role in cancer therapy because of its high specificity, good tolerance and so on. There are different kinds of molecular targeted drugs such as monoclonal antibodies and small molecular kinase inhibitors, and more than 50 drugs have been approved since 1997. When the first monoclonal antibody, rituximab, was on the market. The development of molecular target-based cancer therapeutics has become the main approach. Based on this, we summarized the drugs approved by FDA and introduced their mechanism of actions and clinical applications. In order to incorporate most molecular targeted drugs and describe clearly various characteristics, we divided them into four categories: drugs related to EGFR, drugs related to antiangiogenesis, drugs related to specific antigen and other targeted drugs. The purpose of this review is to provide a current status of this field and discover the main problems in the molecular targeted therapy.
Angiogenesis Inhibitors ; Antibodies, Monoclonal ; Drug Delivery Systems ; Humans ; Molecular Targeted Therapy ; Neoplasms ; drug therapy ; Protein Kinase Inhibitors ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors

Objective To study role of MDC/CCI22-CCR4 axis in mouse milky spots with peritoneal carcinomatosis of gastric cancer. Methods We examined the expression of CCR4 in 615 Mouse gastric cancer cell (MFC) lines by RT-PCR and Western-blot; Peritoneal metastasis model on the 615mouse was established by intraperitoneal injection of 0.2 ml MFC cells(1×104 cells). Dil fluorescence was used to observe the transfer process and section of MFC. Immunohistochemistry was conducted to detect the expression of CCR4 and CCL22 in omental milky spot; the structure of Milky spot was observed by scanning electron microscopy. Mice were randomly divided into 2 groups, namely, the saline control group (received saline) and MFC group. The concentration of CCL22 in ascitic fluid was measured in the 615 mice injected MFC after 6,8,10 days and in the saline group. Results MFC first metastasizes to the milky spot on the omentum, the expression of CCR4 and CCL22 were observered in the milky spot. The surface layer cells in milky spot consisted of discontinuous mesothelial cells and mainly macrophages and lymphocytes. The average value of CCL22 was 43 pg/ml and 364 pg/ml respectively in saline control group and MFC group.Conclusions MDC/CCL22-CCR4 axis plays an important role in the development of peritoneal carcinomatosis in mouse gastric cancer.

Objective To study the role of MDC/CCL22-CCR4 axis in milky spots in peritoneal carcinomatosis of gastric cancer.Methods We examined the expression of CCR4 in 5 gastric cancer cell lines by RT-PCR and Western-blot.Cell growth rate of BGC-823 cell lines before and after incubated with CCL22 was detemined by MTT assay.The effects of CCL22 on invasion of BGC-823 cells into Matrigel were measured using Transwell test.Immunohistochemistry was conducted to detect the expression of CCR4.Results CCR4 mRNA and protein expression were detected in all 5 human gastric cancer cell lines:CCL22had a direct promotive effect on BGC-823 cell prolifetation and invasion.There was CCR4 expression in Stomach neoplasms.The expression of CCR4 in primary tumor was correlated with tumor pathological differentiation(P<0.05),but not with age of patients,gender,location of tumor,tumor size,tumor stage,lymph node metastasis(P>0.05).Conclusions The MDC/CCL22-CCR4 axis may be one of the mechanism of peritoneal metastasis in milky spot in gastric cancer.

Medicinal values and their chemical bases of Paris (Trilliaceae) are reviewed. Paris plants include 40 species and varieties. Among them, 18 ones are medicinal plants with similarity in traditional uses. Fourteen species have been studied phytochemically, which led to isolation of 207 compounds including 121 steroidal saponins. These saponins are major active constituents from Paris plants, which can explain the traditional uses of the plants to treat cancer, malignant boil, bleeding, gastritis, and so on. The similarity in medicinal uses and chemical constituents of Paris plants implies the possibility of resource substitution among these species. It is worth to further investigate Paris plants in chemical constituents, pharmacological activity, biological property, and toxicology.
Animals ; Drug Therapy ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; Magnoliopsida ; chemistry ; Plants, Medicinal ; chemistry

Objective To investigate the effect of insulin-like growth factor-1 (IGF-1) on intercellular adhesion molecule-1 (ICAM-1) expression in rat model with congestive heart failure (CHF). Methods The model of CHF in male Sprague-Dawley rat was established using subcutaneous injection of isoproterenol. The rats were randomized into model group (n = 10),angiotensin converting enzyme inhibitors (ACEI) group ( n=10) and IGF- 1 group ( n = 10). The rats injected with saline were used as normal controls (n=10). The haemodynamic parameters of rats in each group were detected. The concentration of plasma angiotensin Ⅱ (Ang Ⅱ ) and expression of ICAM-1 in rat myocardium were determined by radioimmunoassay and immunohistochemistry,respectively. Results Compared with model group, ACEI and IGF-1 could rescue the diversities of hemodynamic parameters. In addition, ACEI and IGF-1 could also significantly down-regulated concentration of plasma Ang Ⅱ and inhibited ICAM-1 expression. Compared with ACEI, IGF-1 more significantly inhibited ICAM-I expression (0. 804 ± 0. 024 vs. 1. 254 ± 0. 059) and down-regulated concentration of plasma AngⅡ [(369.2±65.0) μg/L vs. (384.4±56.2) μg/L]. Conclusions IGF-1 can suppress ICAM-1 expression in rat model with CHF induced by isoproterenol. This effect may be related to inhibiting activation of RAS system.

Objective To study the therapeutic effects of human umbilical cord mesenchymal stem cells (hUCMSCs) on acute liver failure ( ALF) induced by D-galactosamine (D-gal) and lipopolysaccharide (LPS) in rats. Methods The ALF model was obtained through intraperitoneal injection of D-gal(300 mg/kg)and LPS (20μg/kg)in Wister rats. The hUCMSCs were transplanted after intoxication. All rats were divided into four groups, and each group received either hUCMSCs or 0.9% NaCl solution through intraperitoneal or tail-intravenous injection. To evaluate the liver function of each group, the levels of alanine aminotransferase (ALT), total bilirubin (TBil) and serum albumin (Alb) were measured on the day of hUCMSCs transplantation and the following 1, 2, 3, 5 and 7 days. All rats were then sacrificed to examine the liver histology at day 7. Analyses were done by using Fisher's exact test, unpaired t test and Mann-Whitney U test. Results There were no significant differences of survival rates among four groups (Fisher's exact test, both P = 1. 00). The levels of ALT, TBil and Alb in group receiving hUCMSCs intraperitoneally were (804. 9 ± 88. 0) U/L,(17. 4±2. 7) μmol/L and (20. 9±0. 8) g/L, respectively after 2 days of injection, whereas in the corresponding control group, those were (1294. 3± 171. 4) U/L, (32. 3±5. 5) μmol/L and (16. 1±0. 9) g/L, respectively, which indicated that hUCMSCs transplantation significantly improved the liver function (t = 2. 640, P =0.020;t=2.529, P = 0. 025;t= - 3. 833, P = 0. 002). Both of hUCMSCs-transplanted groups showed no significant differences. Liver histological data showed that transplantation of hUSMSCs through either intraperitoneal or tail-intravenous injection alleviated liver damage (U=4. 500, P = 0. 005;U=4. 500, P = 0. 008) and the mitotic index also increased in hUCMSCs-transplanted groups (U=4. 000, P = 0. 005; U=5. 500, P = 0. 013). Conclusions The levels of ALT, TBil and Alb can rapidly normalize in ALF rats after injected with hUCMSCs either intraperitoneally or tail-intravenously. hUCMSCs application raises the mitotic index, enhances hepatocellular regeneration and improves histological status.

OBJECTIVETo systematically review the efficacy and safety of sodium ferulate (SF) for the treatment of diabetic nephropathy.

METHODSBy computerized retrieving the Cochrane Library, MEDLINE, EMBASE, CNKI, VIP, CBM (theses, conference and internet materials), as well as data from internet materials regarding randomized controlled clinical trials of sodium ferulate for the treatment of diabetic nephropathy were collected completely. Data were strictly extracted using the simple evaluation method recommended in Cochrane Handbook and Meta-analysis was performed using Revman 5.0 software.

RESULTSFourteen randomized controlled trials involving 906 patients met the inclusion criteria. Meta-analysis showed that as compared with the control group, the effects in SF group were superior in terms of reducing urinary albumin excretion rate (UAER) at early stage [WMD = 16.08, 95% confidence interval (95% CI): 11.01 to 21.15] and clinical stage (WMD = 82.66, 95% CI: 66.95 to 98.37), urinary endothelin/endothelin-1 (ET/ET-1, WMD = 10.78, 95% CI: 8.18 to 13.39), levels of serum creatinine (SCr, WMD = 6.42, 95% CI: 1.83 to 11.01), blood urea nitrogen (BUN, SMD = 1.45, 95% CI: 0.19 to 2.71) and total cholesterol (TC, WMD = 0.84, 95% CI: 0.56 to 1.21, as well as in increasing high density lipoprotein-cholesterol (HDL-C, WMD = 0.17, 95% CI: 0.09 to 0.26), showing significant difference between groups. However, the effects of SF were insignificantly different to those of control in reducing fasting blood glucose (FBG, WMD = 0.17, 95% CI: -0.03 to 0.37) and triglyceride (TG, SMD = -0.13, 95% CI -0.49 to 0.23).

CONCLUSIONSAt present the evidences show that SF is superior to the conventional treatment in reducing UAER, ET, SCr, BUN, TC and increasing HDL-C, but there is no evidence to show that SF is superior in reducing FBG and TG. However, the evidence is not strong enough due to the low quality of included literature. More large-scale, multi-center, randomized trials are needed to confirm the efficacy and safety of SF in treating diabetic nephropathy.

Coumaric Acids ; therapeutic use ; Diabetic Nephropathies ; drug therapy ; Humans ; Phytotherapy

OBJECTIVEThe aim of this study was to investigate the effect of 5-aza-2'-deoxycytidine (5-Aza-dc), a methylation inhibitor, on cisplatin-resistance in non-small cell lung cancer cell line A549/DDP and to explore its possible mechanism.

METHODSMTT assay was used to test the cytotoxicity of 5-Aza-dc on A549/DDP cells, and the IC(50) and cisplatin resistance index of A540/DDP cells at 48 hours after 5-Aza-dc (0 µmol/L, 20 µmol/L, 40 µmol/L) treatment at different concentrations. MSP, fluorescence quantitative RT-PCR (real-time RT-PCR) and Western blot were used to detect the hMLH1 methylation status, mRNA and protein expressions, respectively.

RESULTSThe IC(50) value of cisplatin in A549/DDP cells was 30.15 ± 0.76 µmol/L. The MTT assay results demonstrated that during the 5-Aza-dc treatment for 48 hours, the dose of 20 µmol/L was non-toxic and 40 µmol/L was low-toxic. 5-Aza-dc at those two doses reduced IC(50) value of cisplatin to 16.54 ± 0.35 µmol/L (RI = 1.82) and 6.82 ± 0.16 µmol/L (RI = 4.42), respectively. MSP, real-time RT-PCR and Western blot showed that 5-Aza-dc at non-toxic and low-toxic doses removed the partial hMLH1-hypermethylation, and up-regulated hMLH1 mRNA and protein expressions.

CONCLUSIONSLow dose 5-Aza-dc can partially reverse the cisplatin-resistance in A549/DDP cells, which may be achieved through removal of hMLH1 hypermethylation and increased expression of hMLH1 gene. 5-Aza-dc may have a role in increasing the efficacy of chemotherapy for patients whose tumors are lack of hMLH1 expression because of hMLH1 promoter hypermethylation.

Adaptor Proteins, Signal Transducing ; genetics ; metabolism ; Antimetabolites, Antineoplastic ; administration & dosage ; pharmacology ; Azacitidine ; administration & dosage ; analogs & derivatives ; pharmacology ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Cell Line, Tumor ; Cisplatin ; pharmacology ; DNA Methylation ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm ; Humans ; Lung Neoplasms ; metabolism ; pathology ; MutL Protein Homolog 1 ; Nuclear Proteins ; genetics ; metabolism ; Promoter Regions, Genetic ; genetics ; RNA, Messenger ; metabolism

This study aims to perform a survey of genetic variation in neuraminidase (NA) gene of influenza A/H3N2 virus, as well as related resistance to NA inhibitors, in Qinghai Province of China, 2010 to 2012. Strains of influenza A/H3N2 isolated during an influenza survey from 2010 to 2012 in Qinghai were enrolled by random sampling. Viral RNA was extracted and amplified by RT-PCR. Purified PCR products were sequenced thereafter. Genetic analysis of nucleic acid and the derived amino acid sequences was performed by MEGA 4.0. Phylogenetic trees were also constructed. Strains isolated during 2010-2011 in this study clustered closely with World Health Organization (WHO) 2010-2012 reference vaccine strain A/Perth/16/2009 and 2008-2010 reference vaccine strain A/Brisbane/10/2007 on the phylogenetic tree, while the 2012 isolates were located on another branch. In analysis of derived amino acid sequences, the 2010 isolates mutated at K81T, the 2011 isolates mutated at I26V and D127N, while the 2012 isolates mutated at E41K, P46A, I58V, T71N, L81P, D93G, D127N, D151N, and I307M. The D151N mutation added a glycosylation site to the activity center of NA. No significant variation was discovered in H3N2 NA gene of 2010-2011 isolates in Qinghai, China. Isolates of 2012 were found with significant mutation, which has the potential of inducing minor resistance to NA inhibitors like zanamivir and oseltamivir.
Amino Acid Sequence ; China ; Humans ; Influenza A Virus, H3N2 Subtype ; classification ; enzymology ; genetics ; isolation & purification ; Influenza, Human ; virology ; Molecular Sequence Data ; Neuraminidase ; chemistry ; genetics ; Phylogeny ; Sequence Alignment ; Viral Proteins ; chemistry ; genetics

Carcinoma, Hepatocellular ; genetics ; metabolism ; DNA Methylation ; DNA Restriction Enzymes ; metabolism ; DNA, Neoplasm ; genetics ; Glutathione S-Transferase pi ; genetics ; metabolism ; Humans ; Liver Neoplasms ; genetics ; metabolism ; Polymerase Chain Reaction ; methods