iloprost and Adenocarcinoma-of-Lung

Lung cancer remains an important target of cancer research, and accounts for most deaths of any cancer type in the United States. Chemoprevention refers to the use of agents to prevent the development of cancer in high-risk populations, often in patients with predisposing lesions. In the following, we describe our ongoing work examining the role of the eicosanoid prostacyclin in lung cancer chemoprevention. Our findings include the fact that most adenocarcinomas lose the expression of prostacyclin synthase through methylation silencing. In addition, transgenic mice with overexpression of prostacyclin synthase are protected from tumorigenesis in multiple preclinical lung cancer models. Our phase IIb clinical trial using iloprost, a prostacyclin analogue, showed the reversal of airway dysplasia in high-risk individuals. This trial represents the first to show regression of airway dysplasia from the administration of a chemoprevention agent and forms the basis for future trials in lung cancer chemoprevention.

Topics: Adenocarcinoma of Lung; Animals; Anticarcinogenic Agents; Cell Line, Tumor; Cell Transformation, Neoplastic; Clinical Trials, Phase II as Topic; Cytochrome P-450 Enzyme System; Humans; Iloprost; Intramolecular Oxidoreductases; Lung Neoplasms; Mice; Molecular Targeted Therapy; Mutation; PPAR gamma; Signal Transduction; Treatment Outcome; Xenograft Model Antitumor Assays

Systemic sclerosis (SSc) is a chronic disease of unknown etiology which affects the vascular system and connective tissue. A wide series of studies showed an increased prevalence of cancer in patients with SSc than the normal population. Prostacyclin (PGI2) is an endogenously produced element that is basically synthesized by arachiodonic acid through prostacyclin synthesis in vascular system endothelial cells. Iloprost is a stable analogue of PGI2 which is used in the treatment of pulmonary arterial hypertension (PAH). In a limited number of animal models, the anti-metastatic activity of PGI2 is observed. Herein, we report iloprost treatment of a 60-year-old-woman with SSc, who lately developed PAH as a complication of her disease and lung adenocarcinoma as a co-incidence simultaneously. These two mortal complications were both treated successfully with inhaled iloprost until her death due to gastrointestinal complications of SSc.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Administration, Inhalation; Antihypertensive Agents; Antineoplastic Agents; Biopsy; Disease Progression; Familial Primary Pulmonary Hypertension; Fatal Outcome; Female; Gastrointestinal Diseases; Humans; Hypertension, Pulmonary; Iloprost; Immunohistochemistry; Lung Neoplasms; Middle Aged; Multimodal Imaging; Positron-Emission Tomography; Scleroderma, Systemic; Tomography, X-Ray Computed; Treatment Outcome; Vasodilator Agents