Abstract: Methods and composition for delivery of enzymes to a subject's airway. In some aspects, nebulized composition of enzymes, such as plasminogen activators are provided. In further aspects perfluorocarbon compositions comprising enzymes, such as plasminogen activators are provided. Compositions may, in some aspects, be used for the treatment of lung infections or acute lung injury, such as inhalational smoke induced acute lung injury (ISALI).

Abstract: In fibrotic lung fibroblasts, basal levels of p53 protein (and miR-34a) are markedly suppressed, leading to reduced p53-mediated inhibition of uPA and uPAR, or concurrent induction of PAI-1. These changes contribute to excessive FL-fibroblast proliferation and production of extracellular matrix (ECM), and, therefore, pulmonary fibrosis. These processes are reversed by treating the cells, and treating subjects suffering from idiopathic pulmonary fibrosis (IPF) with the small organic molecule nutlin-3a (NTL) or with a peptide, CSP-4 (SEQ ID NO:1), or variants or derivatives or multimers of this peptide, which increase p53 levels by inhibiting MDM2-mediated degradation of p53 protein. Use of these compounds serves as a new approach to the treatment of IPF, they restore p53 expression and p53-mediated changes in the uPA-fibrinolytic system in FL-fibroblasts and restrict production and deposition of ECM.

Abstract: The influence of TF, endothelial cell protein C receptor (EPCR) and protease activated receptor-1 (PAR1) on tumor growth of malignant pleural mesothelioma (MPM) is disclosed. MPM cells that lack or express TF, EPCR or PAR1 and a murine orthotopic model of MPM led to the discovery that intrapleural administration into nude mice of REN MPM cells expressing TF and PAR1 but lacking EPCR and PAR2 generated large pleural cavity tumors. Suppression of TF or PAR1 expression markedly reduced tumor growth. Overexpression of TF in non-aggressive MPM cells expressing EPCR and PAR1 but exhibiting minimal levels of TF failed to alter their tumorigenicity. Introduction of EPCR expression in aggressive MPM cells attenuated tumor growth whereas EPCR silencing in non-aggressive MPM cells overexpressing TF increased tumorigenicity of non-aggressive cells. Expression of EPCR by MPM cells suppresses tumor growth and treats MPM.

Abstract: During lung injury, p53 expression increases, inducing plasminogen activator inhibitor-1 (PAI-1) while inhibiting expression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR), resulting in apoptosis of lung epithelial cells (LECs). In the bleomycin lung injury model, p53 and PAI-1 are induced while uPA and uPAR are inhibited. A 20 residue peptide DGIWKASFTTFTVTKYWFYR termed PP-1 (the Cav-1 scaffolding domain) or peptide NYHYLESSMTALYTLGH, termed PP-2, protected LECs from bleomycin-induced apoptosis in vitro and in vivo and prevented subsequent pulmonary fibrosis by attenuating lung epitheilial damage. Pharmaceutical compositions, peptide multimers and deliverable polypeptides comprising the above peptides are dislcosed.

Abstract: During lung injury, p53 expression increases, inducing plasminogen activator inhibitor-1 (PAI-1) while inhibiting expression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR), resulting in apoptosis of lung epithelial cells (LECs). In the bleomycin lung injury model, p53 and PAI-1 are induced while uPA and uPAR are inhibited. A 20 residue peptide DGIWKASFTTFTVTKYWFYR termed PP-1 (the Cav-1 scaffolding domain) or peptide NYHYLESSMTALYTLGH, termed PP-2, protected LECs from bleomycin-induced apoptosis in vitro and in vivo and prevented subsequent pulmonary fibrosis by attenuating lung epitheilial damage. Pharmaceutical compositions, peptide multimers and deliverable polypeptides comprising the above peptides are dislcosed.

Abstract: The present invention relates to methods of preventing or decreasing the severity of scarring in a subject comprising: obtaining a pharmaceutical composition comprising a single chain urokinase plasminogen activator molecule (scuPA) or a scuPA mimetic; and administering the pharmaceutical composition to a subject; wherein scarring in the subject is either prevented or decreased relative to an amount of scarring that would be expected if the pharmaceutical composition were not administered to the subject. The invention also relates to methods of screening for compounds that prevent or decrease the severity of scarring in a subject.

Abstract: The present invention provides methods for treating inflammatory diseases, neoplastic diseases, wound healing and preventing scarring by administering a therapeutically effective amount of phosphoglycerate phosphokinase (PGK) peptide, polypeptide, protein, mutant or mimetic to a subject. The invention also relates to methods of screening for compounds for modulation of uPAR expression or activity. The present invention further provides coding sequences of phosphoglycerate kinase peptides, polypeptides, or proteins, or mutants, or mimetics thereof as a gene therapy for inflammatory diseases, cancer, wound healing, or tissue scarring.

Abstract: The present invention relates to the use of modified factor VI[ for manufacture of medicaments for treatment of Acute Lung Injury (ALI) or Acute Respiratory Distress Syndrome (ARDS) in humans.

Abstract: The present invention relates to methods of preventing or decreasing the severity of scarring in a subject comprising: obtaining a pharmaceutical composition comprising a single chain urokinase plasminogen activator molecule (scuPA) or a scuPA mimetic; and administering the pharmaceutical composition to a subject; wherein scarring in the subject is either prevented or decreased relative to an amount of scarring that would be expected if the pharmaceutical composition were not administered to the subject. The invention also relates to methods of screening for compounds that prevent or decrease the severity of scarring in a subject.