1.Anti-angiogenesis effect of arsenic trioxide plus cinobufacin on human hepatocarcinoma transplantation model nude mice.
Lin LIU ; Bao-an CHEN ; Shu-kui QIN
Chinese Journal of Integrated Traditional and Western Medicine 2011;31(1):67-72
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
2.Oxaliplatin plus capecitabine as a second line chemotherapy for patients with advanced gastric cancer.
Jun QIAN ; Shu-kui QIN ; Jing-feng MEI ; Ying-xia CHEN ; Zhi-jian SHAO ; Ze-ming HE
Chinese Journal of Oncology 2004;26(12):746-748
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
3.Efficacy and safety of Erlotinib in the treatment for advanced non-small cell lung cancer in Chinese patients.
Yi-long WU ; Mei-lin LIAO ; Shu-kui QIN ; Yan SUN ; Cai-cun ZHOU
Chinese Journal of Oncology 2010;32(2):148-151
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
4.Exploration of differential expressed genes involved in the development and progression of hepatocellular carcinoma using oligo microarray.
Xiu-feng LIU ; Rui-hua SHI ; Heng-jun GAO ; Hong ZHU ; Shu-kui QIN ; Xue-hao WANG
Chinese Journal of Hepatology 2006;14(11):824-827
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
6.Study on the relationship between polymorphism sites of IL-10 and the susceptibility of endometriosis.
Bang-shun HE ; Jing-yan XIE ; Yu-qin PAN ; Yu-juan LI ; Shu-kui WANG
Chinese Journal of Preventive Medicine 2010;44(7):602-606
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
7.Effects of rosuvastatin on left ventricular cardiac function, arteriosclerotic plaque and high sensitive C-reactive protein in hypertensive patients with mild LDL-C elevation.
Ze-peng LIN ; Zhi-wei ZHANG ; Rong-kui ZHANG ; Ping-chun SHU ; Shi-qin WU
Journal of Southern Medical University 2010;30(3):588-590
OBJECTIVETo observe the effect of rosuvastatin on left ventricular cardiac function, arteriosclerotic plaque and high sensitive C-reactive protein (hs-CRP) in hypertensive patients with mild elevation of LDL-C.
METHODSSeventy-nine patients with a SBP of 140-179 mmHg and/or a DBP of 90-109 mmHg and mild elevated LDL-C were treated with rosuvastatin for 12 months (n=40) or not (n=39). The changes of hs-CRP, arteriosclerosis plaque and cardiac function at the end of the 12-months treatment relative to the baseline levels were analyzed.
RESULTSAfter 12 months of treatment, LDL-C was decreased by 33.2% in rosuvastatin group but remained unchanged in patients without rosuvastatin treatment. The left ventricular peak filling rate (LVPFR) increased significantly from 1.85 to 2.59 (P<0.05) and the serum levels of hs-CRP reduced significantly (P<0.05) after rosuvastatin treatment. The size of the plaques reduced significantly after a 12-month rosuvastatin therapy.
CONCLUSIONRosuvastatin therapy on the basis of conventional anti-hypertensive drugs can obviously improve the left ventricular diastolic function and produce favorable effects on arteriosclerotic plaques.
Aged ; Arteriosclerosis ; complications ; pathology ; C-Reactive Protein ; metabolism ; Cholesterol, LDL ; blood ; Female ; Fluorobenzenes ; therapeutic use ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; therapeutic use ; Hyperlipidemias ; drug therapy ; pathology ; physiopathology ; Hypertension ; drug therapy ; pathology ; physiopathology ; Male ; Middle Aged ; Pyrimidines ; therapeutic use ; Rosuvastatin Calcium ; Sulfonamides ; therapeutic use ; Ventricular Function, Left ; drug effects
8.Spinal fixed-point rotating reduction in treating lumbar disc herniation by three-dimensional MRI.
Wei FENG ; Tian-You FENG ; Yong-Min BI ; Fei WANG ; Kui XU ; Shu-Qin WANG
China Journal of Orthopaedics and Traumatology 2013;26(6):476-480
OBJECTIVETo observe three-dimensional space position change of nucleus pulposus and nerve root before and after treatment of lumbar disc herniation by spinal fixed-point rotating reduction, and explore the mechanisms.
METHODSTotally 52 patients with L5S1 lumbar disc hernation treated by spinal fixed-point rotating reduction were collected from April 2009 to June 2011. There were 33 males and 19 females with an average age of 34.6 years old (ranged, 19 to 55). Three-dimensional MRI were performed to observe relationship between nucleus pulposus and related nerve root,configuration change of spine and pelvic on coronary MRI.
RESULTSMRI showed relationship between nucleus pulposus and related nerve root mainly located on axillary, shoulder, front and surround. Vertebral displacement disappeared, lumbocrural pain alleviated after manipulative therapy. All patients were followed up from 2 to 28 months with an average of 12 months, and no recurred. All patients recovered work. Nucleus pulposus had no change,while lumbral spinal and pelvic curve changed before and after admission.
CONCLUSIONLumbar disc herniation combined with single (multiple) vertebral displacement,can cause biomechanical properties of nucleus puplosus and related nerve root, while spinal fixed-point rotating reduction can correct vertebral displacement, recover balance between inside and outside of spinal.
Adult ; Female ; Humans ; Imaging, Three-Dimensional ; Intervertebral Disc Displacement ; diagnosis ; diagnostic imaging ; physiopathology ; therapy ; Lumbar Vertebrae ; diagnostic imaging ; physiopathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Radiography ; Rotation ; Young Adult
10.Study on effect of arsenic trioxide on adhesion and invasion of human hepatocarcinoma cells in vitro.
Hai-qing HUA ; Shu-kui QIN ; Jin-hong WANG ; Huiying CHEN
Chinese Journal of Integrated Traditional and Western Medicine 2004;24(10):922-925
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