px-478 and Small-Cell-Lung-Carcinoma

px-478 has been researched along with Small-Cell-Lung-Carcinoma* in 1 studies

Other Studies

1 other study(ies) available for px-478 and Small-Cell-Lung-Carcinoma

Article	Year
Treatment with HIF-1alpha antagonist PX-478 inhibits progression and spread of orthotopic human small cell lung cancer and lung adenocarcinoma in mice. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2010, Volume: 5, Issue:7 PX-478 is a potent small-molecule inhibitor of hypoxia-inducible factor 1alpha (HIF-1alpha). In prior preclinical studies, it had antitumor activity against various solid tumors in subcutaneous xenografts but had no measurable activity against a non-small cell lung cancer (NSCLC) xenograft. To determine the effectiveness of PX-478 against lung tumors, we investigated HIF-1alpha expression in several lung cancer cell lines, both in vitro and in vivo, and treated orthotopic mouse models of human lung cancer with PX-478.. Cells from two human lung adenocarcinoma cell models (PC14-PE6 and NCI-H441) or two human small cell lung cancer (SCLC) models (NCI-H187 and NCI-N417) were injected into the left lungs of nude mice and were randomized 16 to 18 days after injection with daily oral treatment with PX-478 or vehicle for 5 days.. In the PC14-PE6 NSCLC model, treatment with 20 mg/kg PX-478 significantly reduced the median primary lung tumor volume by 87% (p = 0.005) compared with the vehicle-treated group. PX-478 treatment also markedly reduced mediastinal metastasis and prolonged survival. Similar results were obtained in a second NSCLC model. In SCLC models, PX-478 was even more effective. In the NCI-H187 model, the median primary lung tumor volume was reduced by 99% (p = 0.0001). The median survival duration was increased by 132%. In the NCI-N417 model, the median primary lung tumor volume was reduced by 97% (p = 0.008).. We demonstrated that the PX-478, HIF-1alpha inhibitor, had significant antitumor activity against two orthotopic models of lung adenocarcinomas and two models of SCLC. These results suggest the inclusion of lung cancer patients in phase I clinical trials of PX-478. Topics: Adenocarcinoma; Animals; Apoptosis; Blotting, Western; Carcinoma, Non-Small-Cell Lung; Disease Progression; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunoenzyme Techniques; Lung Neoplasms; Lymphatic Metastasis; Male; Mice; Mice, Nude; Mustard Compounds; Phenylpropionates; Small Cell Lung Carcinoma; Survival Rate; Treatment Outcome; Tumor Cells, Cultured	2010

Article

Year

Treatment with HIF-1alpha antagonist PX-478 inhibits progression and spread of orthotopic human small cell lung cancer and lung adenocarcinoma in mice.

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2010, Volume: 5, Issue:7

PX-478 is a potent small-molecule inhibitor of hypoxia-inducible factor 1alpha (HIF-1alpha). In prior preclinical studies, it had antitumor activity against various solid tumors in subcutaneous xenografts but had no measurable activity against a non-small cell lung cancer (NSCLC) xenograft. To determine the effectiveness of PX-478 against lung tumors, we investigated HIF-1alpha expression in several lung cancer cell lines, both in vitro and in vivo, and treated orthotopic mouse models of human lung cancer with PX-478.. Cells from two human lung adenocarcinoma cell models (PC14-PE6 and NCI-H441) or two human small cell lung cancer (SCLC) models (NCI-H187 and NCI-N417) were injected into the left lungs of nude mice and were randomized 16 to 18 days after injection with daily oral treatment with PX-478 or vehicle for 5 days.. In the PC14-PE6 NSCLC model, treatment with 20 mg/kg PX-478 significantly reduced the median primary lung tumor volume by 87% (p = 0.005) compared with the vehicle-treated group. PX-478 treatment also markedly reduced mediastinal metastasis and prolonged survival. Similar results were obtained in a second NSCLC model. In SCLC models, PX-478 was even more effective. In the NCI-H187 model, the median primary lung tumor volume was reduced by 99% (p = 0.0001). The median survival duration was increased by 132%. In the NCI-N417 model, the median primary lung tumor volume was reduced by 97% (p = 0.008).. We demonstrated that the PX-478, HIF-1alpha inhibitor, had significant antitumor activity against two orthotopic models of lung adenocarcinomas and two models of SCLC. These results suggest the inclusion of lung cancer patients in phase I clinical trials of PX-478.

Topics: Adenocarcinoma; Animals; Apoptosis; Blotting, Western; Carcinoma, Non-Small-Cell Lung; Disease Progression; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunoenzyme Techniques; Lung Neoplasms; Lymphatic Metastasis; Male; Mice; Mice, Nude; Mustard Compounds; Phenylpropionates; Small Cell Lung Carcinoma; Survival Rate; Treatment Outcome; Tumor Cells, Cultured

2010