ABSTRACT
As lung cancer has increased to the most common cause of cancer death worldwide, prognostic biomarkers and effective targeted treatments remain lacking despite advances based on patients' stratification. Multiple core cyclins, best known as drivers of cell proliferation, are commonly deregulated in lung cancer where they may serve as oncogenes. The recent expansion of the cyclin family raises the question whether new members might play oncogenic roles as well. Here, we investigated the protein levels of eight atypical cyclins in lung cancer cell lines and formalin-fixed and paraffin-embedded (FFPE) human tumors, as well as their functional role in lung cancer cells. Of the new cyclins evaluated, CNTD2 was significantly overexpressed in lung cancer compared to adjacent normal tissue, and exhibited a predominant nuclear location. CNTD2 overexpression increased lung cancer cell viability, Ki-67 intensity and clonogenicity and promoted lung cancer cell migration. Accordingly, CNTD2 enhanced tumor growth in vivo on A549 xenograft models. Finally, the analysis of gene expression data revealed a high correlation between elevated levels of CNTD2 and decreased overall survival in lung cancer patients. Our results reveal CNTD2 as a new oncogenic driver in lung cancer, suggesting value as a prognostic biomarker and therapeutic target in this disease.
Subject(s)
Cyclins/metabolism , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Up-Regulation , A549 Cells , Animals , Biomarkers, Tumor/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Humans , Male , Mice , Neoplasm Transplantation , Prognosis , Survival AnalysisABSTRACT
Injuries of the laryngotracheal axis caused by prolonged intubation in critically ill patients raise the issue of the timing of tracheotomy in intubated patients. In 1992 a prospective study was begun in intensive care patients with intubation lasting more than 48 hours. Eight months later, post-mortem data on the laryngotracheal axis of deceased patients was added to our prospective study protocol. The study was closed with 125 cases (52 deceased). The clinical data of 73 surviving patients was compared with that of 18 post-mortem cases. The macroscopic results of the post-mortem study are summarized by grading the lesions according to a personal modification of the Lindholm classification. All cases had laryngotracheal injuries. Only 15% of the lesions were located in the tracheal region. Five cases were classified as grade 2, with an average orotracheal intubation of 9 days, 9 cases as grade 3 with 15 days intubation, and 4 cases as grade 4 with 21 days intubation. We concluded that the severity of laryngotracheal injuries in the early post-mortem exploration was related with the duration of intubation.
