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In the period between January 1986 and December 1989 we have studied 60 patients with primitive lung cancer, subdivided in 3 groups according to the therapy: 20 were treated with surgery therapy, 20 with radiotherapy, 20 with chemotherapy. We have been studying a second group since September 1989; this is composed, until now, by 30 patients, subdivided in three groups as above. To each group we added alfa-2b recombinant Interferon at the dose of 3,000,000 i.m. three times a week for three months. We repeated the same therapy after three months. We have demonstrated that the combination alfa-2b recombinant interferon and the surgery therapy, radiotherapy and chemotherapy in patients with primitive lung cancer, can improve the quality of life but it doesn't prolong the duration of life.

The involvement of bronchial vasculature in the airway remodelling occurring in symptomatic smokers with normal lung function and with chronic obstructive pulmonary disease (COPD) has been poorly investigated. An immunohistochemical study was performed on bronchial biopsies taken from 8 non-smokers and 18 smokers divided, according to global health initiative on obstructive lung diseases (GOLD) classification of COPD, into two groups, GOLD 0 and GOLD 2, each of 9 subjects. The number of vessels and the percentage of vascular area in the lamina propria were evaluated by mAb anti-collagen IV. Cellular expression of VEGF and vascular expression of alphavbeta3 integrin were evaluated by the specific monoclonal antibodies. An image processing and analysis system was used to quantify the immunohistochemical data. The number of vessels, the vascular area, the cellular expression of VEGF, the number and percentage of alphavbeta3 positive vessels were significantly higher in GOLD 0 and in GOLD 2 smokers than in non-smokers. The comparison between GOLD 0 and GOLD 2 smokers did show a weak but significantly lower number of vessels in GOLD 2, while the vascular area and the percentage of alphavbeta3 positive vessels did not differ between the two groups. A higher cellular VEGF expression was detected in the GOLD 2 than in the GOLD 0 group. Angiogenesis of bronchial vessels is a component of the airway remodelling occurring in symptomatic smokers with normal lung function and with COPD, it seems independent by the development of airway obstruction and not related to its severity.

Angiogenesis of bronchial vessels and apoptosis of lung structural cells are important mechanisms involved in the development of COPD. Endoglin (CD105), a proliferation-associated protein abundantly present on angiogenic endothelial cells, is strongly expressed in lung carcinoma but its expression in COPD has never been evaluated. Similarly, the airway epithelial expression of Bcl-xL and Fas (CD95), two molecules regulating the apoptosis pathway, has been scarcely investigated in COPD. Our purpose was to verify whether in symptomatic smokers the presence of a contralateral non small cell lung cancer (NSCLC) can influence the degree of bronchial angiogenesis and can be associated to cell cycle modifications occurring in distant apparently normal mucosa. Bronchial biopsies were obtained from two groups of symptomatic smokers: 12 with a contralateral NSCLC and 13 without NSCLC. Vessels in the lamina propria were identified by using mAbs against the pan-endothelial marker CD 31 and the more specific CD 105. Bcl-xL and CD95 expression was evaluated using the respective mAbs. No significant difference in the expression of CD105 by bronchial vessels was detected between the two groups. However, the number of CD105+ vessels was increased in the lamina propria below metaplastic/displastic squamous bronchial epithelium in smokers with NSCLC. Furthermore, preliminar results show a lower expression of Fas and a higher expression of Bcl-xL in the metaplastic/displastic bronchial epithelium of smokers with NSCLC. These results suggest that cell cycle modifications and increased bronchial angiogenesis can be associated to more aggressive preneoplastic lesions.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation due to airway narrowing and loss of elastic recoil. Emphysema is the hallmark of elasticity loss and can be assessed by CT scan by measuring low attenuation areas (LAA). The BODE staging system, including FEV1 and other variables, helps to predict mortality and hospitalization for COPD. Aim: To assess any relationship between BODE index and CT extension of emphysema in mild-to-severe COPD patients. Patients and study design: Thirty-three out of 48 enrolled out-patients were included in the study (M/F: 24/9, mean age±SD: 67±8.9 yrs; smoking history: 34±19 pack/yrs). BODE index and semi-quantitative CT scoring of emphysema were calculated for each patient within two weeks from enrolment. Results: The mean BODE index and CT emphysema score were 4.3±3.2 and 1±1.2, respectively. No emphysema was recorded in 16 (48%) patients; the emphysema score was 1 (less than 25% of LAA) in seven cases, 2 (between 25 and 75%) in 6 cases and 3 (more than 75%) in 3 patients. Severe emphysema (score: 4) was reported in one patient. We found no correlation between the emphysema score and the BODE index (p= 0.348; r=0.168). Similarly, no correlation was found with FEV1, the level of dyspnoea (MMRC score) and the 6-minute walking distance (m). However, a weak inverse correlation was found with the body mass index (p 0.038; r -0.362). Conclusions: Our preliminary results suggest that no correlation exists between BODE index and semi-quantitative CT emphysema scoring. Further efforts better assessing emphysema and other COPD-related pathological abnormalities, i.e. airway remodelling, are needed in larger samples size

H-Prune hydrolyzes short-chain polyphosphates (PPase activity) together with an hitherto cAMP-phosphodiesterase (PDE), the latest influencing different human cancers by its overexpression. H-Prune promotes cell migration in cooperation with glycogen synthase kinase-3 (Gsk-3beta). Gsk-3beta is a negative regulator of canonical WNT/beta-catenin signaling. Here, we investigate the role of Gsk-3beta/h-Prune complex in the regulation of WNT/beta-catenin signaling, demonstrating the h-Prune capability to activate WNT signaling also in a paracrine manner, through Wnt3a secretion. In vivo study demonstrates that h-Prune silencing inhibits lung metastasis formation, increasing mouse survival. We assessed h-Prune levels in peripheral blood of lung cancer patients using ELISA assay, showing that h-Prune is an early diagnostic marker for lung cancer. Our study dissects out the mechanism of action of h-Prune in tumorigenic cells and also sheds light on the identification of a new therapeutic target in non-small-cell lung cancer.