Objective To investigate the effects of caudal type homeobox 2 (Cdx2) silence on reservion of multi-drug resistance of gastric carcinoma cisplantin-resistant cell SGC7901/DDP.Methods Gastric carcinoma cisplantin-resistant cells SCG7901/DDP in the logarithmic phase were cultured in the plate,and were divided into the experimental group [gastric carcinoma cells of SGC7901/DDP were infected with a silent Cdx2-recombinanted lentiviral vector (pLL-Cdx2-shRNA)],the negative control group (gastric carcinoma cells of SGC7901/DDP were infected with empty lentiviral vector) and the blank control group (gastric carcinoma cells of SGC7901/DDP were not treated).The protein and mRNA expressions of Cdx2 and apoptosis related genes like c-myc,cyclin D1 and survivin were detected by the Western blot and reverse-transcription PCR,respectively.The sensitivity of the cells in the 3 groups to adriamycin,5-fluorouracil and cisplatium were assessed by MTT.The pump-out rate of adriamycin,cell cycle distribution and apoptosis of the 3 groups were analyzed using flow cytometry.All measurement data were expressed with mean ± standard deviation.Comparison among multi-groups was done by one-way analysis of variance,and comparison between 2 groups was done by SNK-q test.The enumeration data were analyzed using the chi-square test.Results The relative protein expression levels of Cdx2,c-myc,cyclin D1 and survivin were 0.187 ± 0.060,0.086 ± 0.004,0.016 ± 0.005 and 0.276 ± 0.012 in the experimental group,0.535 ± 0.033,0.379 ± 0.006,0.141 ± 0.003 and 0.672 ± 0.009 in the negative control group,and 0.567 ± 0.014,0.354 ± 0.004,0.162 ± 0.008 and 0.517 ± 0.313 in the blank control group,respectively.The relative protein expression levels of Cdx2,c-myc,cyclin D1 and survivin in the experimental group were significantly lower than those in the negative control group and the blank control group (F =247.385,3.353,597.882,98.628,P ＜0.05).The relative mRNA expression levels of Cdx2,c-myc,cyclin D1 and survivin were 0.184 ± 0.010,0.212 ± 0.022,0.045 ± 0.009 and 0.401 ± 0.027 in the experimental group,0.894 ± 0.056,0.538 ± 0.021,0.163 ±0.009 and 0.824 ± 0.016 in the negative control group,and 0.837 ±0.049,0.545 ±0.032,0.157 ±0.010 and 0.782 ±0.056 in the blank control group,respectively.The relative mRNA expression levels of Cdx2,c-myc,cyclin D1 and survivin in the experimental group were significantly lower than those in the negative control group and the blank control group (F =243.776,161.793,138.523,118.426,P ＜ 0.05).The IC50 values detected by MTT of adriamycin,5-flurouracile and cisplatin to gastroc carcinoma cisplantin-resistant cell SCG7901/DDP were (0.12 ± 0.05) mg/L,(0.52 ± 0.13) mg/L and (0.82 ± 0.13) mg/L in the experimental group,(0.33 ± 0.08) mg/L,(4.10.± 1.25) mg/L and (2.81 ± 0.50) mg/L in the negative control group,(0.39 ±0.15)mg/L,(4.05 ± 1.44) mg/L and (3.28 ± 1.03) rng/L in the blank control group,respectively.The pump-out rates of adriamycin of the experimental group,negative control group,and the blank control group were0.21％,0.37％ and 0.35％.Compared with the negative control group and the blank control group,the IC50values of adriamycin,5-fluorouracil and cisplatin in the experimental group were significantly increased,and thepump-out rate of adriamycin was significantly decreased (F =8.101,13.854,15.159,x2 =7.106,P ＜ 0.05).The ratios of cells in the G0/G1 phase were 17.87％,34.71％ and 37.20％ in the experimental group,negative control group and the blank control group,respectively.Compared with the negative control group and blank control group,the ratio of cells in the G0/Gt was significantly decreased (x2=1.055,P ＜ 0.05).The ratio of cells in the G2/M phase in the experimental group was 11.93％,and the apoptosis rate was 31.13％,which were significantly higher than the negative group (0.26％,16.58％) and the blank control group (0.35％,13.18％) (x2=2.249,11.030,P ＜ 0.05).Conclusions Silent Cdx2 can effectively enhance the sensitivity of the SGC7901/DDP cells and the intracellular accumulation concentration of the drugs.Silent Cdx2 can also reverse the multidrug resistance of the SGC7901/DDP cells.

OBJECTIVETo compare the therapeutic effect and toxicity of chemotherapy, used alone or in combined with Shenqi Fuzheng Injection (SFI), for the treatment of advanced colorectal carcinoma (ACRC).

METHODSOne hundred and fifty-two patients with ACRC were equally randomized by digital table, to the treated group, treated by chemotherapy of FOLFOX regimen combined with SFI, and the control group treated by FOLFOX regimen alone. The therapeutic effect and adverse reaction of the treatment in patients were assessed.

RESULTSThe effective rate (CR +PR) was 63.2% (48/76) in the treated group and 46.1% (35/76) in the control group, showing significant difference between the two groups (P < 0.05). The median survival time in the two groups was 31 weeks and 28 weeks respectively. CD4/CD8 ratio was significantly increased in the treated group (1.56 +/- 0.21, 1.64 +/- 0.28, P < 0.05), but significantly decreased in the control group (1.58 +/- 0.22, 1.46 +/- 0.33, P < 0.01). Quality of life in the former group was higher than that in the latter group (P < 0.05). Times/case of nausea, vomiting, leukopenia occurring in the control group was more than those in the treated group A (P < 0.05).

CONCLUSIONBy combining with SFI, some adverse reactions of chemotherapy (such as nausea, vomiting, leukopenia) and its influence on patients' immunity could be alleviated in treating ACRC, which might enhance the efficacy of chemotherapy, and improve the quality of life and prolong the median survival time in patients.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Colorectal Neoplasms ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Fluorouracil ; therapeutic use ; Humans ; Leucovorin ; therapeutic use ; Organoplatinum Compounds ; therapeutic use ; Quality of Life ; Survival Rate

OBJECTIVETo investigate the effects of E2F-1 gene silencing on the chemosensitivity of human gastric cancer SGC-7901/DDP cells to cisplatin and explore the underlying mechanism.

METHODSGastric cancer SGC-7901/DDP cells were transfected with the recombinant lentivirirus vector Lv-shRNA-E2F-1 for E2F-1 gene silencing, with cells transfected with the control recombinant lentivirirus vector Lv-shRNA-NC as the negative control. MTT assay was used to evaluate cisplatin chemosensitivity of the cells, and the cell apoptosis rate and cell cycle distribution were detected by flow cytometry. The mRNA and protein expressions of E2F-1 and apoptosis-related genes (survivin and Bcl-2) were detected by RT-PCR and Western blotting.

RESULTSMTT assay showed that the IC50 of cisplatin was significantly lowered in Lv-shRNA-E2F-1-transfected cells compared with the negative and blank control cells (P<0.05). Lv-shRNA-E2F-1 transfection caused significant cell cycle arrest in G0/G1 phase and induced obvious cell apoptosis. Compared with Lv-shRNA-NC group and the blank control group, Lv-shRNA-E2F-1 group showed significantly lowered expressions of E2F-1 mRNA by 45.0% and 41.3% and E2F-1 protein by 66.7% and 70.5%, survivin mRNA by 30.3% and 28.7% and survivin protein by 56.5% and 53.6%, and Bcl-2 mRNA by 76.6% and 76.8% and Bcl-2 protein by 74.6% and 79.9%, respectively. No significant difference was found in the measurements between Lv-shRNA-NC group and the blank control group (P>0.05).

CONCLUSIONE2F-1 gene silencing can enhance cisplatin chemosensitivity of gastric cancer SGC-7901/DDP cells possibly by down-regulating survivin and Bcl-2 expressions, suggesting the value of E2F-1 as a new chemotherapeutic target for gastric cancer.

Apoptosis ; Cell Cycle ; Cell Line, Tumor ; drug effects ; Cisplatin ; pharmacology ; Down-Regulation ; E2F1 Transcription Factor ; genetics ; metabolism ; Gene Silencing ; Genetic Vectors ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; RNA, Messenger ; RNA, Small Interfering ; Stomach Neoplasms ; metabolism ; pathology ; Transfection

OBJECTIVETo investigate synergistic killing effect of anti-human DR5 (death receptor 5 of TRAIL) monoclonal antibody (mDRA-6) and adriamycin(Adr) on HL-60 cells.

METHODSmDRA-6 was prepared by immunizing BALB/c mice with DR5 protein. DR5 expression on Adr-treated HL-60 cells was detected by flow cytometry. Morphologic changes of HL-60 cells were observed under fluorescence microscope. Cytotoxic and apoptotic effects of mDRA-6 and Adr on HL-60 cells were measured by MTT analysis. DNA fragmentation was detected by agarose gel electrophoresis.

RESULTSAdr induce DR5 expression on HL-60 cells. Cell budding, chromatin condensation and apoptotic body formation were observed in HL-60 cells treated by mDRA-6 and Adr. Death and apoptosis of these cells and DNA ladder were exhibited on agarose gel electrophoresis.

CONCLUSIONmDRA-6 and Adr have synergistic killing effect on HL-60 cells.

Animals ; Antibodies, Monoclonal ; pharmacology ; Apoptosis ; drug effects ; Dose-Response Relationship, Drug ; Doxorubicin ; pharmacology ; HL-60 Cells ; Humans ; Mice ; Mice, Inbred BALB C ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; immunology ; TNF-Related Apoptosis-Inducing Ligand ; immunology

OBJECTIVETo investigate the effects of E2F-1 gene silencing on multidrug resistance of human gastric cancer SGC7901/DDP cells and its possible mechanisms.

METHODSGastric cancer SGC7901/DDP cells were seeded in 6 well plates and divided into three groups: the experimental group, blank control and the negative control groups. For the experimental group, the SGC7901/DDP cells were transfected with recombinant lentivirus vector (Lv-shRNA-E2F-1), while the negative control with an control lentiviral vector (Lv-shRNA-NC) and the blank control with no treatment. The E2F-1 protein level was analyzed by Western blot. MTT assay was used to detect the half maximal inhibitory concentration (IC50) of three chemotherapy drugs including adriamycin, 5-fluorouracil (5-Fu) and cisplatine (DDP) of the three cell groups. Flow cytometry (FCM) was used to detect the pump-out rate of adriamycin and apoptosis rate of the three cell groups. Semi-quantitative RT-PCR and Western blot were also used to detect the protein and mRNA levels of multidrug resistance-associated genes (MDR1, MRP) and apoptosis-related genes (c-Myc, Skp2, cyclinD1).

RESULTSThe expression of E2F-1 protein in the experimental group was significantly lower than that in the negative control and blank control groups (0.794 ± 0.033 vs. 1.487 ± 0.082 vs. 1.511 ± 0.084, P < 0.01). The IC50 of the three chemotherapy drugs (adriamycin, 5-Fu and cisplatine) in the experimental group was significantly lower than that of the negative control and blank control groups, respectively (P < 0.01). Compared with the negative control and blank control groups, the pump-out rate of adriamycin of the experimental group was significantly declined [(0.16 ± 0.01)% vs. (0.37 ± 0.01)% vs. (0.35 ± 0.02)%, P < 0.01]. However, the apoptosis rate of the experimental group was significantly higher than that of the negative control and blank control groups [(33.82 ± 1.26)% vs. (17.34 ± 0.81)% vs. (13.16 ± 1.06)%, P < 0.01]. The results of RT-PCR and Western blot assays showed that mRNA and protein expressions of five genes (MDR1, MRP, CyclinD1, c-Myc, Skp2) in the experimental group were significantly lower than that in the negative control and blank control groups, respectively (P < 0.01).

CONCLUSIONSE2F-1 gene silencing enhances the chemosensitivity of gastric cancer SGC7901/DDP cells to the chemotherapeutic drugs, directly or indirectly downregulated the expression of MDR1 and MRP, and finally reverses the multidrug resistance of the gastric cancer cells. The mechanism may be associated with the suppression of cyclinD1, c-Myc and Skp2.

ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Antibiotics, Antineoplastic ; pharmacology ; Antimetabolites, Antineoplastic ; pharmacology ; Antineoplastic Agents ; pharmacology ; Apoptosis ; Cell Line, Tumor ; Cisplatin ; pharmacology ; Cyclin D1 ; genetics ; metabolism ; Doxorubicin ; pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; E2F1 Transcription Factor ; genetics ; metabolism ; Fluorouracil ; pharmacology ; Gene Silencing ; Genetic Vectors ; Humans ; Lentivirus ; genetics ; Multidrug Resistance-Associated Proteins ; genetics ; metabolism ; Proto-Oncogene Proteins c-myc ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Recombinant Proteins ; genetics ; metabolism ; S-Phase Kinase-Associated Proteins ; genetics ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; Transfection

OBJECTIVETo sought to engineer and characterize a biodegradable nanoparticles (NPs) containing rapamycin which use poly (lactic-co-glycolic) acid (PLGA) as the carrier matrix and to assess its in vivo release characteristics by local drug delivery system intravascularly.

METHODSRapamycin-loaded PLGA NPs were prepared by an emulsification/solvent evaporation technique, and NPs size distribution was assessed by submicro laser defractometer. The particle morphology was observed by scanning electron microscopy. In vitro release from the NPs was performed in TE buffer at 37 degrees C under rotation utilizing double-chamber diffusion cells on a shake stander. In vivo NPs intravascular local delivery were performed by DISPATCH catheter in New Zealand rabbit abdominal aorta and Chinese experimental mini-pigs coronary artery models.

RESULTSBiodegradable rapamycin loaded PLGA NPs were constructed successfully by emulsification solvent-evaporation technique. The diameter of rapamycin-PLGA NPs was around 246.8 nm with very narrow size distribution, and rapamycin-NPs showed good spherical shape with smooth uniform surface. Rapamycin loaded in NPs were around was 19.42%. Encapsulation efficiency of drug was over 77.53%. The in vitro release of rapamycin from NPs showed that 75% of the drug was sustained released over 2 weeks and controlled release in a linear pattern. After a single 10 minutes infusion of rapamycin-PLGA NPs suspension (5 mg/ml) under 20.27 kPa through DISPATCH catherter in vivo, the mean rapamycin levels at 7 day and 14 day were (2.438 +/- 0.439) and (0.529 +/- 0.144) microg/mg of the dry-weight of the artery segments (2 cm) which local delivery were administrated.

CONCLUSIONSPLGA NPs controlled drug delivery system for intraarterial local anti-proliferative drug delivery can potentially improve local drug concentration and prolong drug residence time in animal model in vivo. It should be appropriate for further study of its therapy efficiency in human.

Animals ; Aorta, Abdominal ; drug effects ; Coronary Vessels ; drug effects ; Drug Carriers ; chemistry ; Drug Delivery Systems ; methods ; Infusions, Intra-Arterial ; Lactic Acid ; chemistry ; Nanoparticles ; chemistry ; Particle Size ; Polyglycolic Acid ; chemistry ; Rabbits ; Sirolimus ; administration & dosage ; pharmacokinetics ; Swine ; Swine, Miniature

OBJECTIVETo analyze the relationship between the early ST resolution magnitude and TIMI flow, MACE and the cardiac function in ST elevated AMI (STEMI) patients after successful primary PCI.

METHODSA total of 120 consecutive patients with STEMI underwent primary PCI within 12 hours after the onset of chest pain were enrolled in this study, the ST segment resolution was calculated and the patients were divided into group A (n = 81, Sigma STE resolved > or = 50%) and group B (n = 39, Sigma STE resolved < 50%). TIMI flow after PCI, clinical events up to 30 days post PCI and cardiac function 30 days post PCI were assessed.

RESULTSLVEF was higher in group A than that of group B (58.6% +/- 7.1% vs. 50.5% +/- 7.1%, P < 0.05). There are fewer patients with Killip III and IV in group A than in group B (1.2% vs. 12.8%, P < 0.05). The incidence of in-hospital MACE was also significantly less in group A than in group B (0 vs. 7.7%, P < 0.001). As expected, there were more patients with TIMI 3 flow (95.1% vs. 79.5%, P < 0.05) and fewer TIMI 2 (4.9% vs. 20.5%, P < 0.05) flow post PCI in group A than in group B and all 3 patients with MACE were group B patients with TIMI 2 flow.

CONCLUSIONEarly ST resolution post PCI represents improved myocardial perfusion and function and is related to a favorable clinical outcome in STEMI patients.

Aged ; Angioplasty, Balloon, Coronary ; Electrocardiography ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; physiopathology ; therapy ; Treatment Outcome ; Ventricular Function, Left

OBJECTIVETo detect changes of serum soluble Apo-1/Fas (sApo-1/Fas) in pancreatic cancer patients and to investigate its clinical value in assessing the effect of chemotherapy.

METHODSThe serum level of sApo-1/Fas in 30 normal control subjects and 58 pancreatic cancer patients were detected using enzyme-linked immunosorbent assay (ELISA), and the sApo-1/Fas level of 48 pancreatic cancer patients, before and after chemotherapy was compared.

RESULTSCompared with the level of the control group, the level of serum soluble Apo-1/Fas was significantly correlated with clinical stage but not with age, sex or pathologic type of pancreatic cancer. It was elevated gradually from stage II to IV (P < 0.01). However, it would obviously decrease in pancreatic cancer patients after chemotherapy (P < 0.01).

CONCLUSIONThe serum soluble Apo-1/Fas may be involved in the development of pancreatic cancer, and it may be used as one parameter to assess the disease status and prognosis of pancreatic cancer patient.

Adenocarcinoma, Mucinous ; blood ; drug therapy ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Pancreatic Ductal ; blood ; drug therapy ; Cisplatin ; administration & dosage ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Disease Progression ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Pancreatic Neoplasms ; blood ; drug therapy ; Prognosis ; Remission Induction ; fas Receptor ; blood

Adult ; Aneurysm, False ; diagnosis ; pathology ; Electrocardiography ; Female ; Heart Ventricles ; pathology ; Humans

Objective:To summarize the clinicopathologic features and clinical diagnosis and treatment experience of retroperitoneal paraganglioma.Methods:This study retrospectively analyzed the clinical, pathological and follow-up data of 39 patients admitted to the First Affiliated Hospital of Xi'an Jiaotong University from 1 Oct 2012 to 1 Oct 2022 for retroperitoneal paragangliomas undergoing resection.Results:There were 19 males and 20 females with tumor being functional in 11 cases (28%) and non-functional in 28 cases (72%). CT angiography showed that the tumors were distributed around the abdominal aorta and inferior vena cava in most cases. All 39 patients underwent tumor rescetion.Patients in laparoscopic group had shorter operation time and postoperative hospital saty compared with open sugery [(135±66)min vs. (194±67)min, t=-2.529, P=0.016; (6.6±2.2)d vs.(9.6±4.8)d, t=-2.096, P=0.043], while there was no statistically significant difference between the two groups in terms of intraoperative blood loss [(152±151)ml vs. (361±608)ml, t=-1.169, P=0.250]. There were no major postoperative complications in the laparoscopic group, and pulmonary infection in 1 case and intestinal obstruction in 1 case in the open group. Thrity-six cases were followed up, ranging from 2 to 115 months, 1 patient in the laparoscopic group died 1 year after surgery due to recurrence and metastasis. In the open group, 1 case recurred 2 years later and was discharged after the second operation, and 1 case died of recurrence 2 years after surgery. Conclusions:Surgery is indicated for retroperitoneal paraganglioma. Adequate perioperative management is the key to the success of the operation. Laparoscopic surgery is superior to open surgery in terms of operation time and postoperative recovery .