OBJECTIVETo study the anti-angiogenesis effect and toxicity of arsenic trioxide (As2O3) plus cinobufacin on transplanted human hepatocarcinoma in nude mice, and the acting mechanism of the treatment was explored as well.

METHODSHuman hepatocarcinoma was transplanted in nude mouse, and the modeled mice were divided at random into 4 groups, 8 in each group. They were treated respectively with normal saline (GA), 2.5 mg/kg As2O3 (GB), 5 mL/kg cinobufacin (GC) and 2.5 mg/kg As2O3 + 5 mL/kg cinobufacin (GD), by intraperitoneal injection for 21 days. The anti-tumor effects was evaluated by estimating general condition of nude mice, tumor size, microvessel density(MVD) level. Expressions of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) in tumor, in tumor tissue of mice as well as pathology of tumor were detected by immunohistochemistry assay, optical microscope, transmission electron microscope (TEM), respectively. Moreover, blood routine and pathological examinations of liver and kidney were performed.

RESULTSThe tumor weight and volume were 0.65 +/- 0.25 g and 0.44 +/- 0.14 cm3 in GB, 0.70 +/- 0.27 g and 0.46 +/- 0.19 cm3 in GC, 0.42 +/- 0.16 g and 0.26 +/- 0.11 cm3 in GD, all significantly lower than those in GA (1.06 +/- 0.25 g and 0.67 +/- 0.17 cm3, P < 0.05). The coefficient of drug interaction (CDI) on tumor weight was 0.97 and that on tumor size was 0.86, all less than 1, showing the synergistic action between the two drugs. Expressions of VEGF and EGFR in tumor as well as the MVD were decreased in GB and GC, and the decreasing of these indices were even more significant in GD. Pathologic examination showed the growth of tumor in GB, GC and GD were all inhibited significantly. No obvious toxicity of the treatments to the hepatic, renal and hematopoietic systems in the nude mice was observed.

CONCLUSIONSAs2O3 and cinobufacini showed synergistic action in inhibiting human hepatocarcinoma in nude mice and the angiogenesis in tumor. Combined use of the two had no obvious toxicity to the hepatic, renal and hematopoietic systems.

Amphibian Venoms ; pharmacology ; therapeutic use ; Angiogenesis Inhibitors ; Animals ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Arsenicals ; pharmacology ; therapeutic use ; Carcinoma, Hepatocellular ; blood supply ; drug therapy ; Cell Line, Tumor ; Drug Synergism ; Humans ; Liver Neoplasms ; blood supply ; drug therapy ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neovascularization, Pathologic ; drug therapy ; Oxides ; pharmacology ; therapeutic use ; Phytotherapy ; Xenograft Model Antitumor Assays

OBJECTIVETo evaluate the effect and toxicity of oxaliplatin combined with capecitabine (Xeloda) as a second-line chemotherapy regimen for patients with advanced gastric cancer.

METHODSTwenty-four patients with advanced gastric cancer who had been treated by multiple chemotherapy regimens presenting poor responses were allotted. LX regimen (oxaliplatin 85 mg/m(2) in 2-hour infusion on D1 and D15, capecitabine 1250 mg/m(2)/d divided in two daily doses given from D1 to D14) was adopted. The cycles were repeated every 28 days. All patients received two or more cycles.

RESULTSAll 24 patients were evaluated after having received 2 to 6 cycles of chemotherapy, totally 92 cycles. The overall response rate was 29.2% (including 2 CR, 5 PR, 10 NC and 7 PD). The time to tumor progression (TTP) was 2 to 18 months (median 5 months), and duration of remission was 4 to 14 months (median 8 months). The major toxicities were bone marrow suppression and nausea/vomiting.

CONCLUSIONOxaliplatin combined with capitabine is effective as a secondary line regimen for patients with advanced gastric cancer. This protocol is active and well tolerated. Further clinical studies are warranted.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Capecitabine ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Drug Administration Schedule ; Female ; Fluorouracil ; analogs & derivatives ; Humans ; Liver Neoplasms ; drug therapy ; secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Staging ; Neutropenia ; chemically induced ; Organoplatinum Compounds ; administration & dosage ; Remission Induction ; Stomach Neoplasms ; drug therapy ; pathology

OBJECTIVETo explore the relationship of the endometriosis susceptibility and polymorphism of up stream of IL-10 promoter at the site of 1082(G→A), 819(C→T) and 592(C→A).

METHODSA total of 214 patients with endometriosis and 160 healthy individuals were enrolled and divided into patient group and control group in this study. The polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) was applied to detect the base transition in the up stream of IL-10 promoter at the site of 1082(G→A), 819(C→T) and 592(C→A). SPSS11.0 software was applied to analysis frequencies of all genotypes.

RESULTSThere was no difference in polymorphism of IL-10-1082 between the endometriosis (AA: 87.90%, GA: 12.10%) and control group (AA: 87.50%, GA: 12.50%). The rate of TT, CT and CC genotype IL-10-819 was the same as the AA, CA and CC individually. There was no difference in the polymorphism of IL-10-819 or IL-10-592 between the endometriosis group (TT or AA: 41.12%, CT or CA: 47.66%, CC: 11.21%) and control group (χ(2) = 5.87, P = 0.053). However, there were significant difference in the genotype of CT of IL-10-819 or CA of IL-10-592 between the endometriosis group and control group (after adjust OR = 1.88, 95% CI = 1.10 - 3.21, χ(2) = 5.24, P = 0.021), and the allele C of IL-10-819 or IL-10-592 were close related with occurrence of endometriosis (OR = 1.42, 95%CI = 1.04 - 1.95, χ(2) = 4.81, P = 0.028). The IL-10 level in the plasma of endometriosis group with genotype of CC (CC), CT (CA) of IL-10-819(-592) were significant higher than those with TT (AA) (CA/CT: (50.12 ± 82.40) pg/ml, CC: (91.00 ± 118.23) pg/ml, TT/AA: (21.45 ± 22.10) pg/ml) (F = 2.492, P = 0.048; F = 1.852, P = 0.008).

CONCLUSIONThe allele C of IL-10-819 or IL-10-592 was close related to the high level expression of IL-10, and it is the risk of the occurrence of endometriosis.

Adult ; Aged ; Case-Control Studies ; Endometriosis ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Interleukin-10 ; genetics ; Middle Aged ; Polymorphism, Restriction Fragment Length ; Young Adult

Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Liver Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Tissue Array Analysis ; Tumor Suppressor Protein p53 ; metabolism

Aged ; Bone Neoplasms ; secondary ; Carcinoma, Hepatocellular ; pathology ; Humans ; Liver Neoplasms ; pathology ; Male ; Paranasal Sinus Neoplasms ; secondary

OBJECTIVETo explore that the arsenic trioxide injection (ATI) has the effect in antagonizing adhesion and invasion of human hepatocarcinoma cells (HCC), and its relevant mechanism.

METHODSHuman hepatocellular carcinoma cell line SMMC-7721 and the high metastatic nude mice human HCC in situ transplantation model was taken as the objects of study, the effects of ATI on the SMMC-7721 cell movement and migration, its adhesion with fibronectin (FN) and endothelial cell (EC), as well as the CD44 and MMP-2 gene protein expression in transplanted tumor of the model mice were observed by means of cell movement and migration test, cell adhesion test and immunohistochemical method.

RESULTSATI could significantly inhibit SMMC-7721 cell movement and migration on FN, adhesion with FN and EC, also could lower CD44 and MMP-2 in cancer cells.

CONCLUSIONATI has the effects of antagonizing hepatocarcinoma cell adhesion and invasion, the mechanism may be related with the action of ATI in lowering CD44 and MMP-2 expression in cancer cells.

Animals ; Antineoplastic Agents ; pharmacology ; Arsenicals ; pharmacology ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Adhesion ; drug effects ; Cell Line, Tumor ; Cell Movement ; drug effects ; Humans ; Hyaluronan Receptors ; metabolism ; Intercellular Adhesion Molecule-1 ; metabolism ; Liver Neoplasms ; metabolism ; pathology ; Matrix Metalloproteinase 2 ; metabolism ; Mice ; Mice, Nude ; Neoplasm Invasiveness ; Oxides ; pharmacology

OBJECTIVETo observe the efficacy and the adverse effects of erlotinib in the treatment for advanced non-small cell lung cancer (NSCLC) in Chinese patients.

METHODSFrom November 2005 to March 2009, a total of 519 patients with unresectable, local advanced, relapsed or metastatic NSCLC were enrolled in the trial. All the patients were treated with erlotinib 150 mg/day until disease progression or intolerable toxicity or for other reasons. The response rate, time to disease progression, overall survival and toxicity were analyzed.

RESULTSOf these 519 patients, 1 case had complete response, 127 cases had partial response and 263 cases had stable disease, resulting in an overall response rate (CR + PR) of 26.7%, disease stable rate of 54.9% and disease control rate (CR + PR + SD) of 81.6%. The median time to progression was 6.44 months and median overall survival was 15.37 months. The major erlotinib treatment-related adverse events (AE) were mild (CTC AE 1/2), only 3 cases had severe adverse effect, 1 case had interstitial lung disease and died of respiratory failure.

CONCLUSIONThe study presents excellent response rates, time to progression and overall survival of erlotinib treatment for advanced NSCLC in Chinese patients, and its adverse events are tolerable.

Asian Continental Ancestry Group ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Diarrhea ; chemically induced ; Disease Progression ; Erlotinib Hydrochloride ; Exanthema ; chemically induced ; Female ; Follow-Up Studies ; Humans ; Lung Diseases, Interstitial ; chemically induced ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Protein Kinase Inhibitors ; adverse effects ; therapeutic use ; Quinazolines ; adverse effects ; therapeutic use ; Receptor, Epidermal Growth Factor ; adverse effects ; antagonists & inhibitors ; therapeutic use ; Remission Induction ; Survival Rate

OBJECTIVESTo analyze the differential expression genes (DEGs) among hepatocellular carcinoma (HCC), para-cancerous tissue (PCT) and normal liver tissue (NLT) and explore the target genes related to the development and progression of HCC.

METHODSThe total RNAs of matched HCC, PCT and NLT of HCC patients were isolated using one step Trizol method. Matched RNAs were qualified using 10 g/L agarose gel electrophoresis and lab-on-chip. cRNAs were synthesized, fluorescence labeled and purified after total RNAs were purified. The RNAs of HCC and NLT, HCC and PCT were hybridized with Agilent oligo microarray (21,074 probes). The fluorescence intensity features were detected by Agilent scanner and quantified by feature extraction software. The selected candidate genes were confirmed by SYBR Green I stained real time RT-PCR.

RESULTS(1) The total RNA, reverse transcription product and fluorescence labeled cRNA were all of high quality; (2) There were 420 up-regulated genes and 552 down-regulated genes among 2-fold DEGs, including DKK1 (dickkopf homolog 1) which was 5-fold up-regulated; (3) The results of real time RT-PCR, using beta-actin as an internal control, showed that the 2-Delta Ct values of DKK1 in HCC, PCT and NLT were 0.089 504, 0.007,65 and 0.000,631 respectively.

CONCLUSION(1) The high throughput and effective Agilent oligo microarray can screen novel therapy targeted genes by analyzing the DEGs in development and progression of HCC; (2) The development and progression of HCC is a complicated process involving multigenes and multiprocedures; (3) DKK1, as a novel gene, is involved in the development and progression of HCC and may be a new therapy target.

Carcinoma, Hepatocellular ; genetics ; pathology ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Humans ; Liver Neoplasms ; genetics ; pathology ; Oligonucleotide Array Sequence Analysis ; RNA, Neoplasm ; genetics

OBJECTIVETo investigate the effect of endostar in controlling ascites tumor formation in mice.

METHODSMouse models bearing ascites tumors were established via intraperitoneal injection of H22 and S180 cell lines. Eighty-eight ICR mice were randomly assigned into 4 groups, namely the control group (0.9% normal saline) and 3 endostar groups with 8 mg/kg endostar administration daily, every other day or every two days. The peritoneal membrane permeability of the mice was assessed using Evan blue staining. The body weight curve of mice was drawn, and the cumulative ascites volume and number of red cells and tumor cells in the malignant ascites were determined. The survival of the mice was evaluated to assess the therapeutic effect of endostar.

RESULTSCompared with the control group, the mice receiving daily endostar injection showed obviously lower ascites accumulation and peritoneal capillary permeability (P<0.05) with reduced count of ascites tumor cells and red cells and tumor burden of the abdominal cavity. The mice with daily endostar injection also showed longer survival than the control group.

CONCLUSIONSContinuous intraperitoneal injection can be the optimal means for endostar administration for treatment of malignant ascites.

Animals ; Carcinoma, Ehrlich Tumor ; blood supply ; Cell Line, Tumor ; Endostatins ; administration & dosage ; pharmacology ; therapeutic use ; Female ; Humans ; Mice ; Mice, Inbred ICR ; Neovascularization, Pathologic ; Recombinant Proteins ; administration & dosage ; pharmacology ; therapeutic use

OBJECTIVETo explore the feasibility of IGF2 imprinting system in target gene therapy for tumors.

METHODSThe mouse H19 enhancer, DMD and promoter H19 were amplified by PCR from mouse genomic DNA and then cloned into the plasmid pDC312. The EGFP and DT-A fragments were amplified by PCR and cloned into the recombinant plasmid, and then the shuttle plasmid were transfected into HEK293 cells together with the adenoviral vector Ad5, namely, Ad-EGFP and Ad-DT-A. Adenovirus hexon gene expression was applied to confirm the presence of adenovirus infections. The effect of the IGF2 imprinting system was tested by fluorescence microscopy. RT-PCR and Western blotting after transfection of the recombinant adenoviral vectors into cancer cells were used to show loss of IGF2 imprinting (LOI) and maintenance of IGF2 imprinting (MOI), respectively. The anti-tumor effect was assessed by MTT and flow cytometry after the HCT-8 (LOI). Human breast cancer cell line MCF-7 (MOI) and human normal gastric epithelial GES-1 (MOI) cell line were transfected with Ad-DT-A in vitro. The anti-tumor effect was detected by injecting the Ad-DT-A in nude mice carrying HCT-8 tumors.

RESULTSThe expression of EGFP protein, DT-A mRNA and DT-A protein were seen to be positive only in the HCT-8 tumor cell line. Infection with Ad-DT-A resulted in obviously growth inhibition in HCT-8 cells (75.4 ± 6.4)% compared with that in the control group, and increased the percentage of apoptosis in the HCT-8 cells (20.8 ± 5.9)%. The anti-tumor effect was further confirmed by injecting the recombinant adenoviruses in HCT-8 tumor-bearing nude mice, and the results showed that the Ad-DT-A inhibited the tumor growth, with on inhibition rate of 36.4%.

CONCLUSIONSThe recombinant adenoviruses carrying IGF2 imprinting system and DT-A gene have been successfully constructed, while Ad-DT-A can effectively kill the tumor cells showing loss of IGF2 imprinting. It might play an important role in future target gene therapy against malignant tumors based on loss of IGF2 imprinting.

Adenoviridae ; genetics ; Animals ; Apoptosis ; Breast Neoplasms ; genetics ; pathology ; Colonic Neoplasms ; genetics ; pathology ; therapy ; Diphtheria Toxin ; biosynthesis ; genetics ; Female ; Genetic Therapy ; methods ; Genetic Vectors ; Genomic Imprinting ; Green Fluorescent Proteins ; biosynthesis ; genetics ; Humans ; Insulin-Like Growth Factor II ; genetics ; metabolism ; MCF-7 Cells ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Peptide Fragments ; biosynthesis ; genetics ; Plasmids ; RNA, Messenger ; metabolism ; Random Allocation ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; Transfection