Cyclooxygenase-2 inhibition decreases primary and metastatic tumor burden in a murine model of orthotopic lung adenocarcinoma

AbstractObjectiveTo assess cyclooxygenase-2 inhibition on primary tumor and mediastinal metastases in a murine model of orthotopic lung adenocarcinoma.MethodsHuman lung adenocarcinoma cells (CRL5908, female nonsmoker with cyclooxygenase-2 expression by Western blot) were implanted under direct visualization through the parietal pleura in the upper lobe of the left lung (2 × 106 cells/animal) of SCID mice. Mice were randomly assigned to 2 groups, either untreated (n = 62) or celecoxib-treated (n = 60). Celecoxib, a selective cyclooxygenase-2 antagonist, was solubilized in the animals' drink (25 mg/kg per day). Mice were arbitrarily killed at 1, 2, 3, and 4 weeks. A blinded observer assessed primary tumor volume and metastatic disease grossly and histologically.ResultsGross metastatic lymph nodes were present at 3 weeks in none of 15 (0%) treated and 12 of 15 (80.0%) untreated animals (P < .0001). Mean primary tumor volumes at 3 weeks for treated mice were 7.9 ± 10.0 mm3 and for untreated mice were 533.1 ± 453.6 mm3 (mean ± SD, P < .0001). Gross metastatic lymph nodes were present at 4 weeks in 3 of 15 (20%) treated and 17 of 17 (100%) untreated animals (P < .0001). Mean primary tumor volumes at 4 weeks for treated mice were 37.1 ± 46.2 mm3 and for untreated mice were 809.6 ± 1226.4 mm3 (mean ± SD, P < .0001). Mean blood levels of celecoxib in treated mice were 236.8 ± 34.2 ng/mL (mean ± SD).ConclusionsCyclooxygenase-2 inhibition results in decreased primary and metastatic tumor burden in a murine model using human lung adenocarcinoma. Cyclooxygenase-2 inhibition has the potential to decrease tumor progression and metastases in patients with lung adenocarcinoma

A decade of living lobar lung transplantation: recipient outcomes

AbstractObjectiveLiving lobar lung transplantation was developed as a procedure for patients considered too ill to await cadaveric transplantation.MethodsOne hundred twenty-eight living lobar lung transplantations were performed in 123 patients between 1993 and 2003. Eighty-four patients were adults (age, 27 ± 7.7 years), and 39 were pediatric patients (age, 13.9 ± 2.9 years).ResultsThe primary indication for transplantation was cystic fibrosis (84%). At the time of transplantation, 67.5% of patients were hospitalized, and 17.9% were intubated. One-, 3-, and 5-year actuarial survival among living lobar recipients was 70%, 54%, and 45%, respectively. There was no difference in actuarial survival between adult and pediatric living lobar recipients (P = .65). There were 63 deaths among living lobar recipients, with infection being the predominant cause (53.4%), followed by obliterative bronchiolitis (12.7%) and primary graft dysfunction (7.9%). The overall incidence of acute rejection was 0.8 episodes per patient. Seventy-eight percent of rejection episodes were unilateral. Age, sex, indication, donor relationship, preoperative hospitalization status, use of preoperative steroids, and HLA-A, HLA-B, and HLA-DR typing did not influence survival. However, patients on ventilators preoperatively had significantly worse outcomes (odds ratio, 3.06, P = .03; Kaplan-Meier P = .002), and those undergoing retransplantation had an increased risk of death (odds ratio, 2.50).ConclusionThese results support the continued use of living lobar lung transplantation in patients deemed unable to await a cadaveric transplantation. We consider patients undergoing retransplantations and intubated patients to be at significantly high risk because of the poor outcomes in these populations