There is a well-established link between inflammation and cancer of various organs, but little data are available on inflammation-associated markers of diagnostic and prognostic clinical utility in pulmonary malignancy. Blood samples were prospectively collected from 75 resectable lung cancer patients before surgery and in a cohort of 1,358 high-risk subjects. Serum levels of long pentraxin 3 (PTX3) were determined by high-sensitivity ELISA. PTX3 immunostaining was evaluated by immunohistochemistry in cancer tissue. Serum PTX3 levels in the high-risk population were not predictive of developing subsequent lung cancer or any other malignancy; however, serum PTX3 values in patients with lung cancer were significantly higher compared with cancer-free heavy smokers. With a cutoff of 4.5 ng/ml, specificity was 0.80, sensitivity 0.69, positive predictive value 0.15 and negative predictive value 0.98. The receiver operating curve (ROC) for serum PTX3 had an area under the curve (AUC) of 83.52%. Preoperative serum PTX3 levels in lung cancer patients did not correlate with patient outcome, but high interstitial expression of PTX3 in resected tumor specimens was a significant independent prognostic factor associated with shorter survival (p < 0.001). These results support the potential of serum PTX3 as a lung cancer biomarker in high-risk subjects. Furthermore, PTX3 immunohistochemistry findings support the role of local inflammatory mechanisms in determining clinical outcome and suggest that local expression of PTX3 may be of prognostic utility in lung cancer patients.Despite advancements in surgery, anesthesiology and the improvement of chemotherapy and radiotherapy regimens, the prognosis for clinically detected lung cancer remains dismal, with overall 5-year survival rates of 5-15%. Even with early-stage disease 30-40% of the patients ultimately relapse and die, 1 suggesting that sophisticated biological mechanisms affect their outcome that are not reflected by pathological stage alone. For such a reason, prognostic markers independent of stage are actively sought.In the last few years, leukocyte counts and blood levels of several inflammation markers have been correlated with lung cancer prognosis 2 or investigated as lung cancer risk predictors. 3,4 The role of inflammation in cancer pathogenesis and progression-that has long been investigated-includes the generation of reactive oxygen/nitrogen species and the secretion of cytokines, chemokines and proangiogenic factors. [5][6][7][8] In lung cancer, in addition to smoking-the predominant risk factor-inflammatory conditions such as chronic obstructive pulmonary disease, 9 pulmonary fibrosis and chronic lung infections 10,11 as well as polymorphisms of inflammatory genes 12 are all associated with an increased risk.

In the last decades the molecular basis of monogenic diseases has been largely unraveled, although their treatment has often remained unsatisfactory. Autosomal recessive osteopetrosis (ARO) belongs to the small group of genetic diseases that are usually treated with hematopoietic stem cell transplantation (HSCT). However, this approach is not effective in the recently identified form carrying mutations in the receptor activator of NF-kB ligand (RANKL) gene. In this subset, therapy replacement approach based on RANKL delivery has a strong rationale. Here we demonstrate that the systematic administration of RANKL for 1 month to Rankl À/À mice, which closely resemble the human disease, significantly improves the bone phenotype and has beneficial effects on bone marrow, spleen and thymus; major adverse effects arise only when mice are clearly overtreated. Overall, we provide evidence that the pharmacological administration of RANKL represents the appropriate treatment option for RANKL-deficient ARO patients, to be validated in a pilot clinical trial. ß

Acute increased concentrations of PTX3 in CSF but not in plasma are related to the occurrence of vasospasm, indicating that measurement of CSF PTX3 associated with the clinical evaluation can improve early diagnosis of this complication.

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