Recombinant Mutant Human Tumor Necrosis Factor versus Pleural Perfusion of Cisplatin in the Treatment of Malignant Pleural Effusions:a Systematic Review / 中国药房

OBJECTIVE:To systematically evaluate therapeutic efficacy and safety of recombinant mutant human tumor necrosis factor(rmhTNF)versus pleural perfusion of cisplatin in the treatment of malignant pleural effusions,and to provide evidence-based reference in clinic. METHODS:Retrieved from PubMed,Cochrane Library,Web of Science,CJFD,Wanfang database,VIP and CBM,RCTs about rmhTNF(trial group)vs. cisplatin(control group)in the treatment of malignant pleural effusions were included. Meta-analysis was conducted by using Rev Man 5.3 statistical software after quality evaluation and data extraction with Cochrane system evaluator manual 5.3.0. RESULTS:A total of 7 RCTs were included,involving 478 patients. Meta-analysis showed that clinical total response rate of trial group [RR=1.43,95%CI(1.27,1.62),P<0.001] was significantly higher than that of control group,with statistical significance. There was no statistical significance in the incidence of gastrointestinal reaction[RR=1.15,95%CI(0.73,1.80),P=0.55],chest pain[RR=1.12,95%CI(0.73,1.73),P=0.60],fever[RR=0.62,95%CI(0.35,1.08),P=0.09] and myelosuppression[OR=0.94,95%CI(0.57,1.54),P=0.79] between trial group and control group. CONCLUSIONS:Pleural perfusion of rmhTNF is significantly better than cisplatin in the treatment of malignant pleural effusions. The incidences of gastrointestinal reaction,chest pain,fever and myelosuppression induced by rmhTNF were similar to those induced by cisplatin.

Effect and mechanism of rmhTNF on gastric cancer cell lines with differentΔ133p53 status / 中国癌症杂志

Background and purpose: Little about the function of p53 isoforms in gastric cancer was reported. This study was designed to explore the role ofΔ133p53 in the effect of recombinant mutant human tumor necrosis factor (rmhTNF) on gastric cancer cells, and provide a new basis for the diagnostics and therapeutics of gastric carcinoma. Methods: MKN45 (withΔ133p53 expression) or SGC7901 (withoutΔ133p53 expression) cells were treated with rmhTNF of different concentrations only or combined with 5-FU (a traditional gastric cancer cellular killer), and the growth inhibition rate and apoptosis was detected by CCK-8 and lfow cytometry. mRNA expressions ofΔ133p53, Gadd45αand CyclinB1 were measured by nested reverse transcription-polymerase chain reaction (nRT-PCR) or real-time polymerase chain reaction(RT-PCR). Results:On MKN-45 cells with positiveΔ133p53 expression, the inhibitory effect of rmhTNF was signiifcant, the inhibition rates of 50 and 500 IU/mL rmhTNF were 24.82%, 72.33%after culturing for 24 h (t=-9.558, P0.05). In apoptosis test, the apopto-sis-enhancing effect of rmhTNF was signiifcant on MKN45 cells, and the apoptosis-enhancing effect of 5-FU was fur-ther promoted signiifcantly by rmhTNF, the apoptosis of rmhTNF (50 IU/mL), rmhTNF (50 IU/mL) combined with 5-FU (25 μg/mL), rmhTNF (500 IU/mL) combined with 5-FU (25 μg/mL) were 18.20%, 48.66%, 59.83%, separately, after culturing for 24 h (F=123.931, P<0.05). In mRNA measurement, down-regulation ofΔ133p53 and CyclinB1, up-regula-tion of Gadd45αwere signiifcant in MKN45 cells treated by rmhTNF alone or combined with 5-FU. In nRT-PCR anal-ysis, the mRNA levels ofΔ133p53 were relatively 0.886, 0.499, 0.330, 0.161 (F=240.927, P<0.01);In real-time PCR analysis, the mRNA levels of Gadd45αwere 1.227, 1.694, 3.394, and the mRNA levels of CyclinB1 were 1.221, 0.722, 0.316, relatively. The expression ofΔ133p53 was positively related to CyclinB1 (r=0.977, P<0.01), but negatively re-lated to Gadd45α(r=-0.950, P<0.01). Conclusion:InΔ133p53 positively expressed MKN45 cells, rmhTNF showed as an effective tumor inhibitor and an enhancer of 5-FU as well, and this effect might be helped by two p53 down-stream molecules CyclinB1 and Gadd45α. The results suggest thatΔ133p53 might be a key target for the biological effect of rmhTNF against gastric cancer.

Clinical effects of recombinant mutant human tumor necrosis factor on the malignant pleural effusion in-duced by lung adenocarcinoma / 医学研究生学报

Objective The study aimed to observe the clinical effects and the adverse reactions of recombinant mutant human tumor necrosis factor-alpha ( rhu-TNF) on the treatment of malignant pleural effusion ( MPE) induced by lung adenocarcinoma . Methods 70 patients with MPE caused by lung adenocarcinoma hospitalized in our department were chosen as the research objects . After conventional drainage of pleural effusion , the patients were divided into two groups according to the weight , respectively receiving intra pleural injection of 2 000 000 units and 3 000 000 units of rhu-TNF, followed by the observation of clinical effects and adverse reac-tions.A further retrospective analysis were made on the effects of dexamethasone injected before operation on clinical effects and ad -verse events. Results The effective rates of 2 000 000 unit group and 3 000 000 unit group were respectively 75.68%and 87.88%(P=0.23), with no statistical difference.The adverse reactions in the group of patients being injected dexamethasone before operation significantly reduced(P=0.021) and the use of dexamethasone had no influence on the efficacy of rhu-TNF ( P=0 .486 ) . Conclusion Rhu-TNF is a safe drug with high efficiency in the treatment of MPE induced by lung adenocarcinoma , and the efficacy and safety of re-peated application in clinic still need more supporting data .

Influence of rmhTNF on the Chemotherapy Treatment of Small Cell Lung Cancer / 华中科技大学学报（医学）（英德文版）

The efficacy and safety of the recombinant mutant human tumor necrosis factor (rmhTNF) combined with chemotherapy vs chemotherapy alone in the treatment of patients with small cell lung cancer (SCLC) were evaluated in this study. The selected 37 patients with SCLC were divided into experimental group (n = 18) and control group (n = 19). Bothgroups were subjected to EP regimen. While in the experimental group, a regimen of 4 × 106 U/m2 rmhTNF intramuscular injection was given once a day from the 1st to 7th day and 11th to 17th day on the chemotherapy cycle.Twenty-one days were as a chemotherapy cycle and all patients received treatment with 2 cycles.The response rate was 83.3 % (15/18) in the experimental group and 63.2 % (12/19) in the control group respectively (P＜0.05). The KPS score after treatment was 78.4±9.6 in the experimental group and 71.2±9.7 in the control group with the difference being significant (P＜0.05).No severe adverse effects occurred in the two groups. It was concluded that the curative effectiveness of the rmhTNF combined with chemotherapy in the treatment of SCLC was more satisfactory than chemotherapy alone. The former could obviously improve the quality of life of the patients with SCLC.

Detection of Hepatitis B Virus Surface Antigen Mutants / 대한진단검사의학회지

BACKGROUND: Mutation in the "a" determinant of HBsAg can alter the hepatitis B virus surface antigen (HBsAg) affinity to anti-HBs, which might escape detection by HBsAg immunoassays. This study was to evaluate the ability to detect the HBsAg mutants of diagnostic kits commonly used in laboratories in Korea. METHODS: Nine different recombinant HBsAg mutant panels provided by Abbott Laboratories (Abbott Park, USA) were assayed by Abbott AxSYM and Bayer ADVIA Centaur (Bayer HealthCare LLC, Tarrytown, USA). The performance of diagnostic kits was investigated through the External Quality Assurance Program of the Korean Association of Quality Assurance of Clinical Laboratory (KAQACL) using a recombinant HBsAg mutant (G145R) also kindly provided by Abbott Laboratories. HBsAg mutation was evaluated in patients' sera, whose results of HBV markers were unusual, using HBV DNA sequence analysis. RESULTS: Although Abbott AxSYM detected all of the nine recombinant mutants tested in this study, Bayer ADVIA Centaur failed to detect D144A and recombinant mutants with 2 mutations including G145R. Seven different diagnostic kits, such as Abbott Architect, AxSYM and IMx, Immulite (DPC, Los Angeles, USA), Cobas Core (Roche Diagnostics GmbH, Mannheim, Germany), BEP (Dade Behring, Marburg, Germany), and VIDAS (bioMerieux, France) used in 70 of the 142 participating laboratories of KAQACL could detect the recombinant HBsAg mutant, G145R. HBsAg mutants in native sera of 2 Korean patients with the concurrent presence of HBsAg and anti-HBs, were also detected easily by Elecsys (Roche Diagnostics GmbH, Mannheim, Germany), ADVIA Centaur, and Axsym. By sequence analysis, one of the patients was found to have I126S mutation and the other patient multiple mutations of Q54R, L98V, and Q101R. CONCLUSIONS: HBsAg mutants are probably more frequent even in normal diagnostic settings than previously believed. Detection of HBsAg needs to be improved by the introduction of new HBsAg assays able to recognize so far described HBsAg mutants and with a lower detection threshold than current immunoassays in order to detect the smallest amounts of HBsAg in low level carriers.

Inhibitory effect of recombinant mutant human tumor necrosis factor combined with cisplatin on transplanted Lewis lung carcinoma in mice / 中国肿瘤生物治疗杂志

Objective:To investigate the inhibitory effect of recombinant mutant human tumor necrosis factor(rmhTNF-?)combined with cisplatin(DDP)against transplanted Lewis lung carcinoma(LLC)in mice,and to explore the related mechanism.Methods:LLC cells were subcutaneously inoculated into C57BL/6 mice at the right axilla and the mice were randomly divided into 4 groups:sodium chloride(control group),DDP group,rmhTNF-? group,rmhTNF-? plus DDP group.On the 7th day after inoculation the diameter of the tumor reached 0.6 cm;the corresponding agents were intratumorally injected for 3 d.All mice were sacrificed 1 d later and the tumors were obtained,weighed,and the tumor inhibitory rate was calculated.Flow cytometric analysis was used to examine cells apoptosis and cell cycle.Expression of survivin mRNA was examined by RT-PCR.Results:(1)The tumor inhibitory rates of the DDP plus rmhTNF-? group(36.61%)was significantly higher than those of the DDP group(17.12%)and rmhTNF-? group(15.83%,P

Recombinant mutant human-TNF in reversing drug-resistance in ovarian cancer cell line SKOV3/DDP and the related mechanism / 中国肿瘤生物治疗杂志

Objective:To investigate the reversing effect of recombinant mutant human tumor necrosis factor (rmh-TNF) on cisplatin(DDP)-resistant human ovarian cancer cell line SKOV3/DDP in vitro and the related mechanism. Methods: DDP-resistant human ovarian cancer cell line SKOV3/DDP was cultured in vitro. The cytotoxic effect of rmh-TNF to SKOV3/DDP cells was examined by MTT assay and the nontoxic dose of rmh-TNF was identified. The changes of DDP resistance was observed after cells were treated with nontoxic dose of rmh-TNF by MTT assay. The expre-ssion of GST-? protein was examined by flow cytometry at different periods after rmh-TNF intervention; RT-PCR was used to analyze the expression of MDR1gene in SKOV3/DDP cells before and after rmh-TNF treatment. Results:(1)rmh-TNF at 50-122.34 U/ml showed no evident inhibitory effect on the growth of SKOV3/DDP cells (the cell survival rate higher than 90%); and 100 U/ml was chosen for the reversing experiment ( nontoxic dose).(2)IC50 values of SKOV3/DDP cells were (23.29?0.43), (8.97?0.69) and (6.43?0.79) ?g/ml after treatment with DDP for 24, 48 and 72 h, respectively; and the values decreased to (19.50?0.50),(4.34?0.43) and (2.44?0.02)?g/ml after combined treatment with 100 U/ml rmh-TNF, respectively.(3)Expression of GST-? protein and MDR1gene decreased with the prolongation of rmh-TNF treatment. Conclusion: rmh-TNF has reversal effect on the DDP-resistant cell line SKOV3/DDP, and the mechanism may be associated with the down-regulation of GST-? protein and MDR1gene expression.

Recombinant mutant human tumor necrosis factor enhances anti-angiogenesis effect of cisplatin on Lewis lung carcinoma in mice / 中国肿瘤生物治疗杂志

Objective: To observe the role of rmh-TNF in enhancing the anti-angiogenesis effect of cisplatin on Lewis lung carcinoma in the mice.Methods: Lewis lung carcinoma model was established in C57BL/6 mice.Sixty model mice were randomly divided into 4 groups: control group,rmh-TNF group(1500000 U/kg),cisplatin group(6.15 mg/kg), and rmh-TNF plus cisplatin group.Twelve days after implantation of cancer cells,different drugs were injected intra- tumorallv for 3d.The expression of hypoxia inducible factor-1?(HIF-1?)gene in the tumor was identified by RT-PCR. Immunohistochemistry(IHC)image analysis was performed to determine the vascular endothelial growth factor(VEGF) and kinase domain region receptor(KDR)expression and the microvessel density(MVD).Expression of matrix metallo- proteinase-2(MMP-2)was detected by flow cytometry.Results: The MVD values in the control group,the rmh-TNF group,the DDP group and the combination group were(24.76?1.28),(18.95?1.22),(19.53?1.15),(10.43?1.05),respectively,with those of the rmh-TNF and DDP groups significantly lower than that of the control group and higher than that of the combination group(all P

Factors affecting the efficacy of rmhTNF for advanced lung cancer with maglignant pleural effusion / 重庆医科大学学报

60,treated with high dose rmhTNF and low quantity of pleural effusion)present fine clinical effect.