BACKGROUND: Microarc oxidation (MAO) is a break-through anodyzing technology for forming oxide films on valve metal.Use of this technology allows thick, porous oxide layers to be formed on the surface of pure titanium. Few biocompatibility reports using this treatment have been found.OBJECTIVE: The blood compatibility of a novel surface modified titanium substrata biomaterial using MAO was investigated.DESIGN: Positive and negative control, contrast observation and gold standard control.SETTING: Wuhan Union Hospital.MATERIALS: A healthy male adult New-Zealand rabbit, weighing 2.5 kg and ordinary grade, was selected in this study.Pure titanium sticks TA1 (Baoji Yingnaite Non-ferrous Metal Co., Ltd.), MAO-Ti and 20 g/L potassium oxalate were also selected in this study.METHODS: The study was carried out in the Laboratory of General Surgery, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology in May 2006. ① Materials: Titanium substrate of 10 mm in diameter and 2 mm in depth was put in an electrolyte which was quipped with deionized water, dibasic sodium phosphate, and ethanoic acid calcium for MAO treatment for 10 minutes. ② Groups: Three groups were analysed: test group, negative control group and positive control group. Test group: MAO-Ti was dipped in 10 mL saline; Positive control group: 10 mL deionized water was added in each tube; Negative control group: 10 mL saline was added in each tube. ③ Operation: Fresh whole blood was collected from rabbit and then mixed with the liquids in the three groups respectively after anti-coagulation. In addition, UV-Visible Spectrophotometer was used to evaluate the hemolytic ratio. A hemolytic ratio below or equal to 5% indicated that this novel material fitted the requirements. On the contrary, a hemolytic ratio higher than 5% proofed the existence of a hemolyzation.MAIN OUTCOME MEASURES: The hemolytic ratio of materials in three groups.RESULTS: The hemolytic ratio of the test group was 0.90%. The result indicated that this new material had no haemolysis effect.CONCLUSION: The material does not resolve red blood cells and is coincident with the international and governmental standard.

OBJECTIVETo investigate the clinical treatment modality and prognosis of small cell lung cancer(SCLC).

METHODWe retrospectively analyzed the clinical data of 77 SCLC patients who were admitted to our department after 2002.

RESULTSThe disease was limited in 43 patients and extensive in 34 patients. For patients with limited SCLC, the 1-year, 2-year, and 5-year survival rate was 80%, 56%, and 21%, respectively. Four patients who had undergone surgical resection were all alive. Among patients who underwent adjuvant chemotherapy followed by radiotherapy, salvage chemotherapy, and salvage chemotherapy followed by radiotherapy, the median of survival period was 51 months, 12 months, and 28 months, respectively. For patients with extensive SCLC, the 1-year and 2-year survival rate was 56% and 25%, respectively. The median of survival period was 14.3 months. Stage was an independent factor in multifactor COX regression. Monofactor COX regression showed that radiotherapy and resection were factors correlated with survival. Brain metastasis had no impact on survival.

CONCLUSIONSChemotherapy followed by radiotherapy is preferred for limited SCLC, while surgical resection remains questionable for early-stage patients. For extensive SCLC, multi-line chemotherapy may be helpful to improve the overall survival. Stage is an independent factor for predicting the prognosis.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Small Cell ; diagnosis ; therapy ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; diagnosis ; therapy ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Analysis

OBJECTIVETo investigate the association of the ratio of regulatory and effector T cells with recurrence and chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSThirty patients with hematological malignancies who underwent allo-HSCT were classified as recurrence with cGVHD (n=4), non-recurrence with cGVHD (n=14), recurrence without cGVHD (n=5) and non-recurrence without cGVHD (n=7). The different percentage of CD4⁺CD25⁻CD69⁺ regulatory T cells in bone marrow and CD4⁺CD25⁺FoxP3⁺ regulatory T cells, Th1 cells and Th17 cells in peripheral blood were analyzed by flow cytometry.

RESULTSThere were no significant differences in all these T-cell subsets among different groups (P>0.05). While the ratio of CD4⁺CD25⁻CD69⁺ regulatory T cells and Th1 cells (0.211±0.177) in 9 recurrence patients was significant higher than that (0.133±0.160) in 21 non-recurrence patients (P=0.033). The ratio were also significance between recurrence without cGVHD and non-recurrence without cGVHD patients (0.167±0.073 vs 0.073±0.057, P=0.048), and between recurrence with cGVHD and non-recurrence without cGVHD patients (0.218±0.113 vs 0.073±0.057, P=0.024). Furthermore, the ratio of CD4⁺CD25⁺FoxP3⁺ regulatory T cells and Th17 cells was significant lower (1.975±2.045) in 18 cGVHD patients than that of 12 without cGVHD patients (3.198±1.132, P=0.010), and the ratio was also significant lower in non-recurrence patients with cGVHD (1.695±1.178) than that of without cGVHD (3.446±1.376, P=0.028).

CONCLUSIONOur results show that the ratio of CD4⁺CD25⁻CD69⁺ regulatory T cells and Th1 cells raise in recurrence patients, and the ratio of CD4⁺CD25⁺FoxP3⁺ regulatory T cells and Th17 decrease in cGVHD patients, which suggest that the ratio of regulatory and effector T cells had association with recurrence and cGVHD in patients with allo-HSCT.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Graft vs Host Disease ; immunology ; pathology ; Hematologic Neoplasms ; immunology ; therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Recurrence ; T-Lymphocytes, Regulatory ; cytology ; immunology ; Transplantation, Homologous ; Young Adult

OBJECTIVETo construct an adenovirus vector expressing TIP30 gene (Ad-TIP30) and investigate its tumor suppressive effect in vitro and in vivo.

METHODSAd-Easy system was used to construct Ad-TIP30 by recombination in E. coli. The virus was packaged in 293 cells and subsequently identified valid. Human HCC (hepatocellular carcinoma) cell lines HepG(2) (p53-wt), PLC/PRL/5 (p53-mut), and osteosarcoma cell line Saos-2 (p53-null) with different p53 genotype were infected with Ad-TIP30 and control virus with Ad-GFP, respectively. The tumor suppressive effect of TIP30 in vitro was examined by trypan blue exclusion method. The expression level of p53 was determined by RT-PCR before and after Ad-TIP30 infection. The in vivo tumor suppressive effect was detected in nude mice with human HCC xenograft.

RESULTSThe expression of TIP30 significantly inhibited the in vitro proliferation of tumor cells, among which HepG(2) with wild type p53 gene was most susceptible to Ad-TIP30 induced growth inhibition. The expression of p53 was significantly up-regulated in HepG(2) after Ad-TIP30 infection as determined by RT-PCR. The growth in nude mice of HCC infected with Ad-TIP30 was significantly inhibited with an inhibition rate of 62.9%.

CONCLUSIONThe expression of TIP30 could inhibit the proliferation of tumor cell lines through both p53-dependent and p53-independent pathways, and may be used as a potential tool for cancer therapy.

Acetyltransferases ; genetics ; Adenoviridae ; genetics ; Animals ; Cell Division ; Genes, p53 ; Genetic Therapy ; Genetic Vectors ; genetics ; Mice ; Neoplasms, Experimental ; genetics ; therapy ; Transcription Factors ; genetics

OBJECTIVETo compare the differences of the T helper cell reconstitution kinetics between HLA matched or HLA mismatched allo-HSCT through exploring the reconstitution kinetics of CD4+ CD25+Foxp3+ cells (CD4+ Treg), CD8+CD25+Foxp3+ cells (CD8+Treg), CD4+CD25-CD127+ conventional T cells (Tcon) and the secretion of IL-17a and IFN-γ in CD4+ T cells (Th17 and Th1 cells) or CD8+ T cells (Tc17 and Tc17 cells) post allogeneic hematopoietic stem cells transplantation (allo-HSCT).

METHODSFrom December 2011 to October 2012, the peripheral blood (PB) of 20 patients undergoing HLA matched (10 patients) or mismatched (10 patients) allo- HSCT without acute graft-versus-host disease (aGVHD) and of 10 related healthy donors were collected to analyze the expression of CD25+Foxp3+, IL-17a, IFN-γ and CD127 expression through 8-colour Flow cytometer.

RESULTS(1) The reconstitution kinetics of CD3+ T cells, CD4+ T cells, CD8+ T cells absolute numbers were comparable within 2 month post HLA matched and mismatched transplantation. (2)The absolute numbers of CD4+ Treg cells[+30 d, 8.46 (0.36-27.41) cells/μl 1.10 (0.04-8.03) cells/μl, P<0.05; +60 d, 8.50 (1.16-36.20) cells/μl vs 2.73 (0.34-6.84) cells/μl, P<0.05], Tcon cells[+30 d, 72.69 (3.85-211.73) cells/μl vs 13.41 (0.48-96.17) cells/μl, P<0.05; +60 d, 100.85 (16.28-267.20) cells/μl vs 47.75 (6.34-143.04) cells/μl, P<0.05], as well as Th17 cells[+30 d, 2.34 (0.02-6.87) cells/μl vs 0.20 (0.02-1.34) cells/μl, P<0.05; + 60 d, 1.90 (0.36- 7.82) cells/μl vs 0.46 (0.03-1.39) cells/μl, P<0.05]and Tc17 cells[+ 30 d, 1.08 (0.07-15.03) cells/μl vs 0.25 (0.01- 0.81) cells/μl, P<0.05;+60 d, 1.85 (0.63-26.57) cells/μl vs 0.46 (0.01-3.66) cells/μl, P<0.05]within 2 month post HLA matched HSCT were significantly higher than those post HLA- mismatched HSCT. However, the absolute numbers of Th1 cells or Tc1 cells within 2 month post HLA-matched or HLA-mismatched HSCT were comparable. (3) The ratio of Th1 and Th17 cells, or the ratio of Tc1 and Tc17 cells were significantly higher within 2 month post HLA-mismatched allo-HSCT compared to those post HLA-matched HSCT.

CONCLUSIONThe reconstitution kinetics of T helper cells subset were different at early stage post HLA-matched or HLA-mismatched allo-HSCT, which might be help to explain the different rate or the different involved organ of the acute graft-versus-host diseases (aGVHD) post HLA-matched or -mismatched allo-HSCT.

Adult ; Female ; HLA Antigens ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; T-Lymphocytes, Helper-Inducer ; T-Lymphocytes, Regulatory ; Th1 Cells ; Th17 Cells ; Transplantation, Homologous ; Young Adult

OBJECTIVECellular senescence as one of the important steps against tumor is observed in many cancer patients receiving chemotherapy and is related to chemotherapeutic response. To investigate the effect of cisplatin on hepatocellular carcinoma, we treated HepG2 cells exhibiting wild-type TP53 with gradient concentrations of cisplatin.

METHODSThe inhibitory effects of cisplatin on human hepatoma HepG2 cells were detected by MTT assay and colony formation test. The changes in cell cycle were analyzed by flow cytometry, and cellular senescence was detected with senescence associated β-galactosidase (SA β-gal) staining. The relative mRNA expression levels of TP53, P21 and P19 was estimated using semi-quantitative real-time RT-PCR, and the protein expressions of P53 and P21 were detected using Western blotting.

RESULTSCisplatin induced irreversible proliferation inhibition and G1 phase arrest of HepG2 cells. Elevated levels of senescence-associated β-galactosidase was observed in HepG2 cells exposed to low doses of cisplatin. P19 expression immediately increased following cisplatin exposure and reached the maximum level at 48 h, followed then by a rapid decrease to the baseline level, whereas the expressions levels of TP53 and P21 mRNA increased continuously. Western blotting confirmed P53 and P21 expression changes similar to their mRNA expressions during cisplatin-induced cellular senescence in HepG2 cells.

CONCLUSIONOur results revealed a functional link between cisplatin and hepatocellular senescence. Cellular senescence induced by cisplatin as a stabile senescent cellular model can be used for further research.

Cell Cycle ; drug effects ; Cell Cycle Checkpoints ; drug effects ; Cellular Senescence ; Cisplatin ; pharmacology ; Cyclin-Dependent Kinase Inhibitor p19 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Hep G2 Cells ; Humans ; Tumor Suppressor Protein p53 ; metabolism ; Up-Regulation

Objective To explore the efficiency of sunitinib in Chinese pancreatic neuroendocrine tumors (pNET) patients. Methods Advanced pNET patients who had accepted sunitinib treatment in the oncology department of PUMC Hospital from January 2009 to June 2015 after disease progression were enrolled in this study. Data collection included clinicopathological characteristics,medical therapies and outcomes. Results Eighteen pNET patients were collected. The overall response rate (ORR) was 27.7% and the disease control rate (DCR) was 83.3%. Nine patients received sunitinib as the first-line therapy and 9 as the second/post-second line. The median progression-free survival (mPFs)(12 month vs. 12 month;HR:0.92,95%CI:0.31-2.75,P=0.88),ORR (22.2% vs.33.3%;Χ(2)=0.055,P=0.98),and DCR (88.9% vs.77.8%;Χ(2)=0.4,P=0.98)showed no significant difference between first-line therapy and post-second line therapy. The mPFS of Ki-67≥10% and Ki-67<10% group patients was not significantly different (8 months vs. 13 months;HR:1.13,95% CI:0.34-3.77,P=0.845). The commonly reported adverse events included bone marrow suppression,diarrhea,roteinuria,hypertension,and rash. Conclusions First-line or second/post-second line sunitinib treatment has certain antitumor activity in Chinese patients with advanced pNET. The efficiency and commonly reported adverse events of Sunitinib are consistent with the known Western data.
Antineoplastic Agents ; therapeutic use ; Disease-Free Survival ; Humans ; Indoles ; therapeutic use ; Pancreatic Neoplasms ; drug therapy ; Pyrroles ; therapeutic use

BACKGROUNDSodium 4-phenylbutanoate (NaPB) can induce cellular differentiation and cell cycle arrest. However, its potential anticancer properties in hepatocellular carcinoma and influence on normal liver cell are still unclear. We observed the effects of NaPB on growth inhibition, including differentiation and phase growth arrest in normal liver cell line L-02 and hepatocellular carcinoma cell line Bel-7402. Furthermore, we investigated its mechanism in Bel-7402. METHODS; Hepatocellular carcinoma cells Bel-7402 and normal liver cell line L-02 were treated with NaPB at different concentrations. Light microscopy was used to find morphological change in cells. Cell cycle was detected by flow cytometry. Expression of acetylating histone H4 and of histones deacetylase 4 (HDAC4) were determined by Western blot. The expression of P21WAF1/CIP1 and E-cadherin were observed through immunocytochemistry.

RESULTSNaPB treatment led to time dependent growth inhibition in hepatocellular carcinoma cells Bel-7402. NaPB treatment caused a significant decline in the fraction of S phase cells and a significant increase in G0/G1 cells. NaPB increased the expression of P21(WAF1/CIP1) and E-cadherin in Bel-7402 and significantly decreased the level of HDAC4 in Bel-7402. NaPB significantly improved the level of acetylating histone H4. The normal liver cell line L-02 showed no distinct changes under treatment with NaPB.

CONCLUSIONSNaPB inhibited the growth of hepatocellular carcinoma cells Bel-7402 and induced partial differentiation through enhancing the acetylating histones. In Bel-7402, the expressions of P21(WAF1/CIP1) and E-cadherin may be related to level of acetylating histones and inhibition of cellular growth. NaPB showed no significant effect on normal liver cells.

Antineoplastic Agents ; pharmacology ; Blotting, Western ; Cadherins ; analysis ; Carcinoma, Hepatocellular ; drug therapy ; metabolism ; pathology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclin-Dependent Kinase Inhibitor p21 ; analysis ; Enzyme Inhibitors ; pharmacology ; Histone Deacetylase Inhibitors ; Humans ; Liver Neoplasms ; drug therapy ; metabolism ; pathology ; Phenylbutyrates ; pharmacology

OBJECTIVETo evaluate the efficacy and safety of weekly paclitaxel combined with S-1 or fluorouracil in the first line treatment of advanced gastric carcinoma.

METHODSTwo hundred and forty patients with untreated advanced gastric carcinoma were randomized into two arms, patients in the experimental arm were given paclitaxel and S-1, while those in the control arm received paclitaxel and fluorouracil. The regimen of experimental arm was paclitaxel 60 mg/m(2) by intravenous infusion, day 1, 8, 15; S-1 80 - 120 mg/day given by oral administration, day 1 - 14. The regimen of control arm was fluorouracil 500 mg/m(2) by intravenous infusion continuously, day 1 - 5; CF 20 mg/m(2) by intravenous infusion, day 1 - 5. The regimens in both arms were repeated every 28 days. The efficacy and safety of both arms were assessed.

RESULTSTwo hundred and twenty-eight patients were analyzed in the full analysis set, and 192 patients were analyzed in per-protocol set (experimental arm 100 patients, control arm 92 patients). The overall response rates of experimental and control arms were 50.0% and 28.3% (P = 0.002), and the disease control rates were 82.0% and 70.7% (P = 0.064), respectively. The primary endpoints of experimental arm were non-inferior to that of the control arm. The secondary endpoint of experimental arm in terms of median progression free survival was significantly better than that of control arm (5 months versus 4 months, P = 0.006). The experimental arm had a higher incidence of grade III-IV bone marrow suppression than the control arm, but the incidence of fever in both arms was not significantly different.

CONCLUSIONSOral administration of S-1 is an alternative option of venous infusional fluorouracil. Weekly paclitaxel combined with S-1 is a safe regimen and has a promising efficacy.

Adenocarcinoma ; drug therapy ; pathology ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Squamous Cell ; drug therapy ; pathology ; Diarrhea ; chemically induced ; Disease-Free Survival ; Drug Combinations ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; Male ; Middle Aged ; Neoplasm Staging ; Oxonic Acid ; administration & dosage ; adverse effects ; Paclitaxel ; administration & dosage ; adverse effects ; Prospective Studies ; Remission Induction ; Stomach Neoplasms ; drug therapy ; pathology ; Survival Rate ; Tegafur ; administration & dosage ; adverse effects

Objective To evaluate the irnmunogenicity, safety and stability of the manufacture process regarding three consecutive lots of influenza split vaccines (Anflu ). Methods A double-blind, randomized and controlled clinical trial was conducted in healthy volunteers. A total of 566 subjects aged 18 to 60 years were recruited and stratified into four age groups before randomly assigned into four groups. Each group would receive one dose of influenza vaccine from either one of the three lots ofAnflu or one lot of the licensed control vaccine. Each dose of the vaccines contained 15 μg of each of the H1N1, H3N2 and B type antigen. Safety was assessed through 30-minute observation for immediate allergic reaction and three-day observation after vaccination. HI antibody titers were determined before vaccination and on day 21, after vaccination. Results Mild adverse reaction was reported and the overall incidence rates on fever of the four groups were from 1.4% to 2.8% but no significant difference was observed between groups. Seroconversion rates of the three viral strains in four groups were 80.3% and above with fold increase as≥11.1 and protection rate was≥93.4%. For the three lots of investigated vaccines, all of the indexes of the three viral strains in four groups exceeded the standards on EMEA and FDA for influenza vaccine. Conclusion The three consecutive lots of Anflu appeared to be good, with both consistent immunogenieity and safety, indicating the stability of manufacture process.