A systematic analysis of orphan cyclins reveals CNTD2 as a new oncogenic driver in lung cancer.

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.

[Spirometry is a good method for detecting and monitoring chronic obstructive pulmonary disease in high-risk smokers in primary health care]. / La espirometría es un buen método para la detección y el seguimiento de la EPOC en fumadores de alto riesgo en atención primaria.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a common disease, the early diagnosis of which allows effective management and treatment. The aim of the present study is to show the effectiveness of a screening and monitoring plan for COPD in high-risk patients in primary health care. PATIENTS AND METHODS: The subjects in this prospective observational longitudinal study comprised 164 high-risk smokers aged between 40 and 76 years. Age, sex, weight, height, and smoking habit (pack-years) were recorded and spirometry was performed according to the guidelines of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR). Patients were informed of their results and given brief advice on how to stop smoking. After 3 years, the patients underwent the same evaluation. RESULTS: In 1999, 22% of the smokers were diagnosed with COPD. Three years later, an additional 16.3% were diagnosed as having COPD, and the disease had worsened in 38.8% of those already diagnosed. Of the patients with a forced expiratory volume in one second (FEV1) less than 90%, 44.8% developed COPD (relative risk: 10.54). An accelerated decrease in FEV1 was found in 18.1% of the patients (20.7% with COPD and 9.0% without COPD). Mean tobacco consumption in 1999 was 28.1 pack-years in subjects without COPD and 31.7 pack-years in those with COPD, whereas in 2002, consumption was 30.6 pack-years in patients with COPD and 31.9 pack-years in those without. In 3 years, 22.8% had stopped smoking (20.5% without COPD and 30.3% with COPD). CONCLUSIONS: Many smokers managed to give up smoking after learning their spirometric results. FEV1 can identify smokers at greatest risk of developing COPD. Spirometric screening and monitoring of smokers at high risk in primary health care can identify those most susceptible to developing COPD while the disease is in an early phase. Therefore the most appropriate strategy can be adopted for each patient.

An Excel spreadsheet computer program combining algorithms for prediction of protein structural characteristics.

A program running on personal computers (either Apple Macintosh or PC, using Excel worksheets) for the prediction of some protein structural characteristics is reported. The program runs according to the Chou and Fasman algorithm, with some modifications, for secondary structure prediction. The program also incorporates several complementary analyses for secondary structure prediction to help the user in the decision-making process: rules for amino acid preferences in the N-cap and C-cap of alpha-helices; prediction of the protein structural class and search of sequential motifs related to secondary structure. Additional algorithms performed by the program are: prediction of domain boundaries, prediction of loops, prediction of the state of cysteines (reduced or in disulfide bridge), hydropathy profiles according to Kyte and Doolittle, Hoop and Woods, and flexibility plot according to Karplus and Schulz.

Glycogen metabolism in a Saccharomyces cerevisiae phosphoglucose isomerase (pgil) disruption mutant.

Disruption of the gene pgil of Saccharomyces cerevisiae, which codes for phosphoglucose isomerase, results in a dramatic increase in the amount of intracellular glycogen in early exponential cultures. The level of glucose 6-phosphate was much higher in mutant than in wild-type cells. Phosphorylase a activity and the state of activation of glycogen synthase were also investigated. Phosphorylase a activity was rather low along the culture in wild-type cells, whereas it was consistently higher in mutants. Glycogen synthase was mostly in the active form in early-medium exponential cultures in wild-type cells whereas the activation state of this enzyme in mutant cells, although lower at the earlier steps of the culture, did not differ from wild-type cells at later stages. The fact that the intracellular levels of UDP-glucose are markedly increased in mutant cells suggest that the observed accumulation of glycogen results from a rise in substrate availability rather than from the activation of the enzyme responsible for the synthesis of the polysaccharide.

Glycogen hyperaccumulation in Saccharomyces cerevisiae ras2 mutant. A biochemical study.

The mechanism by which yeast ras2 mutant hyperaccumulates glycogen has been investigated. Total glycogen synthase activity was between 2.5 and 1.3 times higher in the ras2 mutant than in an isogenic strain. In addition, while in the normal strain the glycogen synthase activation state decreased along the exponential phase, in the mutant strain the opposite behaviour was observed: glycogen synthase activation state rose continuously reaching full activation at the beginning of the stationary phase. Glycogen phosphorylase a activity was up to 40 times higher in the mutant than in the normal strain. Glucose 6-phosphate and fructose 2,6-bisphosphate levels were slightly more elevated in the mutants. The increase in total glycogen synthase and, particularly, the full activation of this enzyme may explain glycogen hyperaccumulation in the ras2 mutant even in the presence of elevated levels of glycogen phosphorylase a.