Tumstatin185-191 increases the sensitivity to cisplatin in a cisplatin-resistant human lung adenocarcinoma cell line / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effects and related mechanisms of Tumstatin 185-191 as a single agent or in combination with cisplatin on proliferation and apoptosis in a cisplatin-resistant human lung adenocarcinoma cell line A549-DDP cells.</p><p><b>METHODS</b>A549-DDP cells were treated with Tumstatin185-191 and cisplatin at varying concentrations. Cell viability was assessed by a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. 50% inhibiting concentration (IC(50)) values of the chemotherapeutic drugs were analyzed by MTT assay. Cell apoptosis was measured by flow cytometry. The activation of Akt and ERK was evaluated by Western blotting.</p><p><b>RESULTS</b>Tumstatin185-191 inhibited the proliferation of A549-DDP cells and its IC(50) value was 80.25 micromol/L. After cotreatment with 20 micromol/L Tum185-191, the IC(50) value of cisplatin in A549-DDP cells reduced from 77.16 micromol/L to 57.97 micromol/L, the reverse index was 1.33, while with 40 micromol/L Tumstatin185-191 the IC(50) was reduced from 77.16 to 26.40 micromol/L and the reverse index was 2.92. The early apoptosis rate was 19.5% +/- 1.1% in the cotreatment group, while 13.3% +/- 1.5% in cisplatin group and 10.2% +/- 2.0% in Tum185-191 group (F = 4.09, P < 0.05). The levels of phospho-Akt (p-Akt) and phospho-ERK (p-ERK) in the A549-DDP cells were remarkably lower after treatment with Tumstatin 185-191. The Tumstatin 185-191 treatment alone or in combination with cisplatin had a similar effect on the protein levels of p-Akt and p-ERK in A549-DDP cells.</p><p><b>CONCLUSION</b>Our data suggest that Tumstatin185-191 may promote apoptosis, downregulate proliferation and partly reverse the drug resistance of A549-DDP cells to cisplatin. The effects induced by Tum185-191 may be mediated through inactivation of the Akt and ERK pathways.</p>

Application of sequential noninvasive following invasive mechanical ventilation in COPD patients with severe respiratory failure by investigating the appearance of pulmonary-infection-control-window / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the application of sequential noninvasive following invasive mechanical ventilation in chronic obstructive pulmonary disease (COPD) patients with severe respiratory failure by investigating the appearance of pulmonary-infection-control-window.@*METHODS@#From November 2001 to October 2004, 76 case of COPD patients with severe respiratory failure due to pulmonary infection were intubated and recruited in the study. When the pulmonary infection was significantly controlled (the time of pulmonary infection control was called PIC window) by the antibiotic and comprehensive therapy, all cases were randomized into noninvasive veatiation group (NIV) and control group. The early extubation was conducted and followed by noninvasive mechanical ventilation via facial mask with bilevel positive airway pressure mode immediately in the NIV group. Conventional invasive synchronized intermittent mandatory ventilation (SIMV) plus pressure support ventilation (PSV) was used as the weaning technique in the control group.@*RESULTS@#Thirty eight cases among 76 patients were in the NIV group, and the rest in the control group. The NIV group and the control group had similar age, sex, APACHE scores, RR, HR, MAP, PaO2 and PaCO2 at the time of commencement and PIC window (P > 0.05). The time of PIC window was (7.5 +/- 1.9) d in the NIV group, and (8.0 +/- 2.5) d in the control group (P > 0.05). In the NIV group, the durations of invasive mechanical ventilation (MV) and total MV were (7.5 +/- 1.9) d and (12.5 +/- 4.0) d respectively, while the durations were (23.5 +/- 9.5) d in the control group (P < 0.05). The durations of RICU stay and hospital stay were shorter than that in the control group. The incidence of ventilation associated pneumonia (VAP) was 18.4% (7/38) in the NIV group, 39.5% (15/38) in the control group respectively (P < 0.05). The incidence of reintubation was 13.2% (5/38) in the NIV group, 34.2% (13/38) in the control group respectively (P < 0.05). Hospital mortality was 7.9% (3/38) in the NIV group, and 28.9% (11/38) in the control group (P < 0.05).@*CONCLUSION@#In those COPD patients requiring intubation and mechanical ventilantion who have severe respiratory failure due to pulmonary infection, sequential noninvasive following invasive mechanical ventilation at the appearance of PIC window can significantly reduce the MV duration, the length of RICU stay and hospital stay, and decrease the occurrence of VAP, reintubation and hospital mortality as well. So it is an efficient strategy to be generalized.