[The effect of intrapleural pingyangmycin administration on activity of fibrinolytic system and transforming growth factor-beta1 in malignant pleural effusion].
OBJECTIVE
To observe the changes of the concentrations of plasminogen activator inhibitor-1(PAI-1), tissue-type plasminogen activator(t-PA), transforming growth factor-beta(1)(TGF-beta(1)) in peripheral blood and pleural effusion before and after intrapleural pingyangmycin administration, and therefore to investigate the mechanism by which pingyangmycin produces pleurodesis.


METHODS
Since February to September 2008, a total of 26 patients with malignant pleural effusion (MPE) underwent intrapleural pingyangmycin administration. The concentrations of PAI-1, t-PA, TGF-beta(1) and the number of leucocytes in peripheral blood and pleural effusion before and after treatment were detected. The pleurodesis efficacy according to WHO standard was evaluated 1 month later. Patients who showed complete disappearance of pleural effusion lasting more than 1 month and reduction of pleural effusion more than 50% were classified as the effective group, while the others were classified as the failure group.


RESULTS
One month after intrapleural pingyangmycin administration, the total response rate of MPE control was 57.7% (effective group = 15 cases). The number of leucocytes and neutrophils in peripheral blood were significantly higher after intrapleural pingyangmycin administration [the number of leucocytes: effective group (9.2 +/- 2.0) x 10(9)/L, failure group (9.4 +/- 3.8) x 10(9)/L; neutrophil count: effective group (7.9 +/- 2.1) x 10(9)/L, failure group (8.1 +/- 3.3) x 10(9)/L] than in those before[the number of leucocytes: effective group (6.6 +/- 1.4) x 10(9)/L, failure group (5.6 +/- 0.9) x 10(9)/L; neutrophil count: effective group (4.5 +/- 1.3) x 10(9)/L, failure group (4.2 +/- 1.0) x 10(9)/L. F = 30.80, 46.08 respectively, all P < 0.01]. However, the concentrations of PAI-1, t-PA and TGF-beta(1) in the peripheral blood showed no significant difference before and after treatment(P > 0.05). The concentrations of PAI-1 were significantly lower in the pleural effusion before treatment [effective group (1054 +/- 1039) microg/L, failure group (1027 +/- 955) microg/L] than after treatment [24 h after intrapleural pingyangmycin administration: effective group (2195 +/- 861) microg/L, failure group (1099 +/- 568) microg/L]; 72 h after treatment: effective group (1688 +/- 703) microg/L, failure group (1383 +/- 797) microg/L(F = 6.29, P = 0.01). The levels of t-PA were significantly higher in the pleural effusion before treatment [the effective group (42 +/- 33) microg/L, failure group (54 +/- 25) microg/L] than after treatment[24 h after intrapleural pingyangmycin administration: the effective group (49 +/- 49) microg/L, failure group (53 +/- 40) microg/L; 72 h after treatment: the effective group (17 +/- 20) microg/L, failure group (28 +/- 22) microg/L (F = 19.85, P < 0.01). The levels of TGF-beta(1) in the pleural effusion showed no significant difference before and after treatment (P > 0.05). The number of leucocytes in pleural effusion was significantly higher after intrapleural pingyangmycin administration [the effective group (4.7 +/- 4.7) x 10(9)/L, failure group (2.1 +/- 1.4) x 10(9)/L] than before [the effective group (2.3 +/- 1.9) x 10(9)/L, failure group (1.0 +/- 0.9) x 10(9)/L. F = 8.05, P < 0.01]. The number of leucocytes, neutrophils and the concentrations of PAI-1, t-PA, TGF-beta(1) in the peripheral blood showed no significant difference between the effective group and the failure group before and after treatment (P > 0.05). However, the concentrations of PAI-1 in pleural effusion after treatment were higher in the effective group than in the failure group (F = 8.51, P < 0.01).


CONCLUSIONS
Intrapleural pingyangmycin administration is a safe and effective treatment for MPE. The mechanism of pleurodesis is related to inhibiting the activity of plasminogen in the pleural cavity.
Zhu
Qing-Qing
QQ
Department of Respiratory Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Sun
Geng-Yun
GY
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D001761:Bleomycin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D016066:Pleural Effusion, Malignant / Q000188:drug therapy* / Q000378:metabolism*; D018700:Pleurodesis / Q000379:methods; D011446:Prospective Studies; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D017395:Plasminogen Activator Inhibitor 1; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; C025703:bleomycetin; D010959:Tissue Plasminogen Activator