Controlling malignant pericardial effusion by intrapericardial administration of recombinant mutant human tumor necrosis factor in patients with carcinoma

Objective: To evaluate the therapeutic efficacy of injecting recombinant mutant human tumor necrosis factor (rmhTNF) into pericardial cavity of carcinoma patients with malignant pericardial effusion. Methods: In 20 cases of malignant pericardial effusion, the intrapericardial catheter was inserted into pericardial cavity, and then rmhTNF of 1.5 × 107 U was infused. The infusion was repeated every 5-7 days with the total 4-6 times. If the effusion disappeared, rmhTNF was then used 2 more times and then the intrapericardial catheter was pulled out. Results: Of 20 patients, 14 were complete response (CR), 4 were partial response (PR) and 2 no change (NC). The disappearance of effusion in 6 cases lasted for more than 6 months. Conclusion: Injecting rmhTNF into pericardial cavity may be a better way to control malignant pericardial effusion and has mild side effects.

Effect of tumor necrosis factor-α on ventricular arrhythmias in rats with acute myocardial infarction in vivo

Acute myocardial infarction （AMI） is an acute cardiovascular emergency. This study was undertaken to assess the effect of tumor necrosis factor-a （TNF-a） on ventricular arrhythmias induced byAMI in rats in vivo. Two hundred and forty male Wistar rats were randomized into a sham- operation group, an AMI group, and a recombinant human tumor necrosis factor receptor：Fc fusion protein（rhTNFR：Fc） group. Acute anterior wall myocardial infarction was produced in the AMI group by ligating the left anterior descending coronary artery （LAD）, and there was no ligation but operation in the sham-operation group. The rhTNFR：Fc group was treated with rhTNFR：Fc（10 mg/kg）, a TNF-a antagonist, 24 hours before LAD ligation. The spontaneous and induced programmed electrical stimulation ventricular arrhythmias were recorded at baseline and 10 minutes, 20 minutes, 30 minutes, 60 minutes, 3 hours, 6 hours and 12 hours after ligation. At the same time the protein and mRNA expression levels of TNF-a among different groups were detected by histochemistry and real-time fluorescent quantitative PCR. Expression of TNF-a increased markedly from 10 minutes after infarction, peaked at 20-30 minutes, and returned to baseline gradually in the AMI group and rhTNFR：Fc group. The time- windows of spontaneous and induced ventricular arrhythmias were similar. Compared with the AMI group, the rhTNFR：Fc group showed a lesser expression of TNF-a protein and a lower incidence of ventricular arrhythmias （P〈0.05）. There was no obvious change in the sham-operation group. The expression of TNF-a induced by AMI could contribute to the onset of ventricular arrhythmias.

Influence of rmhTNF on the Chemotherapy Treatment of Small Cell Lung Cancer

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）. Both groups were subjected to EP regimen. While in the experimental group, a regimen of 4 × 10^6 U/m^2 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.

THE DEVELOPMENT OF MONOCLONAL ANTIBODY AGAINST rhTNF AND ITS CURATIVE EFFECTSON E.Coli INFECTED MICE

Fifteen hybridoma cell lines producing monoclonal antiboclies (McAb) against recombinant human tu-mor necrosis factor a (rhTNFa) have been established by fusing SP 2/0 cells with spleen cells from aBALB/c mouse immunized with rhTNFa. Following J M Davis’s Works, semi-solid medium was usedfor initial cloning. Five of them were studied further. Their main chromosome- numbers range were 96 to105, all of them were IgG1 subclass. The affinities of these McAbs were estimated to be 1. 25 ×108 mol/L, 1. 12×108 mol/L, 2. 34×108 mol/L, 8. 55 × 107 mol/L, 1. 04×108 mol/L, respectively.Two groups of mice challenging with E Coli (107 organisms), one group treated with 2mg/kg anti-TNF monoclonal antibody, the other did not. There was a higher survival rate in treated group, the serumTNF level was significantly lower too, and the untreated mice had severe pathologic changes in vlscera.