P-selectin glycoprotein ligand-1 (PSGL-1) is up-regulated on leucocytes from patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by a dysregulated recruitment of circulating leucocytes into the lung which is associated with the onset and progress of the disease. P-selectin glycoprotein ligand-1 (PSGL-1) is expressed on leucocytes and plays an essential role in primary leucocyte-endothelial cell adhesive contacts. The present study investigated if PSGL-1 is up-regulated on leucocytes of COPD patients. Peripheral blood samples were collected from COPD patients as well as controls (smoking, nonsmoking volunteers) and subjected to analysis of PSGL-1 expression on leucocytes, i.e. neutrophils, eosinophils, monocytes and lymphocytes by flow cytometry. No significant difference was observed between healthy nonsmoking and healthy smoking control subjects. In contrast, PSGL-1 expression was found to be significantly increased on the surface of all four leucocyte populations in COPD patients compared to both control groups. The finding that PSGL-1 surface expression is up-regulated on leucocytes of COPD patients as compared to leucocytes of controls suggests PSGL-1 as a potential target for anti-inflammatory treatment.

[Bronchial artery embolisation using platinum coils in 52 patients with severe pulmonary hemorrhage]. / Bronchialarterien-Embolisation mit Platin-Coils bei 52 Patienten mit schwerer pulmonaler Blutung.

BACKGROUND: Severe pulmonary hemorrhage ist life-threatening. One of the treatment options in case of severe pulmonary hemorrhage is bronchial artery embolisation (BAE) with different embolisation materials. PATIENTS AND METHODS: Efficacy of BAE using platinum coils was investigated retrospectively in a total of 52 patients. 22 suffered from benign lung diseases (angiodysplasia, inflammation, bronchiectasia) and 30 patients had lung cancer (lung metastases in two cases). RESULTS: Primary hemostasis was achieved in over 90 % of the patients (47 of 52). Recurrent BAE was necessary in 23 % of patient with benign etiologies and in 50 % of the tumor patients. Comparing the results of the lung cancer patients with a control group from a teaching hospital without BAE we found survival-advantages for those patients treated with BAE. CONCLUSION: Our results underline the usefulness of BAE in severe pulmonary hemorrhage.

Nuclear YB-1 expression as a negative prognostic marker in nonsmall cell lung cancer.

The human Y-box binding protein, YB-1, is a multifunctional protein that regulates gene expression. Nuclear expression of YB-1 has been associated with chemoresistance and poor prognosis of tumour patients. Representative samples from autopsied material of primary tumours from 77 patients with NSCLC were investigated by immunohistochemistry for subcellular distribution of YB-1 and p53, in order to evaluate the prognostic role of nuclear expression of YB-1. Cytoplasmic YB-1 expression was found in all tumour samples, whereas nuclear expression was only observed in 48%. There was no correlation with histological classification, clinical parameters or tumour size, stage and metastasis status. However, patients with positive nuclear YB-1 expression in tumours showed reduced survival times when compared with patients without nuclear expression. Including information about the histology and mutational status for p53 increased the prognostic value of nuclear YB-1. Patients with nuclear YB-1 expression and p53 mutations had the worst prognosis (median survival 3 months), while best outcome was found in patients with no nuclear YB-1 and wildtype p53 (median survival 15 months). This suggests that the combined analysis of both markers allows a better identification of subgroups with varying prognosis. Nuclear expression of Y-box binding protien seems to be an independent prognostic marker.

Adenovirus-mediated E2F-1 gene transfer in nonsmall-cell lung cancer induces cell growth arrest and apoptosis.

Since overexpression of E2F-1 has been shown to induce apoptosis, the ability of adenovirus-mediated transfer of E2F-1 to inhibit tumour growth in nonsmall-cell lung cancer cell lines was investigated. Three cell lines with various genomic status were infected with AdE2F. Cell proliferation and viability were determined by trypan blue exclusion. Apoptosis induction was assessed by flow cytometry and poly-adenosine diphosphate-ribose-polymerase cleavage assay. In vivo, the effect of E2F-1 on tumour growth was determined in severe combined immunodeficiency (SCID) mice. The current experiments showed that overexpression of E2F-1 suppressed tumour cell growth. The population of apoptotic cells was dramatically increased 96 h after infection with AdE2F. Inhibition of cell growth and induction of apoptosis was not dependent on genomic status. Moreover, treatment of implanted tumours in SCID mice with AdE2F inhibited tumour growth. These data suggest that adenovirus-mediated E2F-1 gene therapy may be effective in the treatment of nonsmall-cell lung cancer.

BAX and p16INK4A are independent positive prognostic markers for advanced tumour stage of nonsmall cell lung cancer.

Clinical studies suggest prognostic relevance of p16INK4A in nonsmall cell lung cancer (NSCLC) while conflicting results for p53 have been published. However, the importance of the apoptosis regulating gene BAX, a downstream regulator of p53, on the prognosis of NSCLC is unknown. The present study investigated the prognostic relevance of BAX with respect to the status of p53 and P16INK4A in 61 patients with advanced NSCLC. Protein expression of BAX, p53 and p16INK4A was investigated retrospectively by immunohistochemistry. Tumour deoxyribonucleic acid (DNA) was screened for p53 mutations by single strand-conformation polymorphism polymerase chain reaction (PCR) and BAX frameshift mutations by fragment length analysis. Patients with positive BAX protein expression had a significantly longer median survival (14 months) than those patients without BAX expression (6 months, p=0.0004). In contrast, p53 status did not influence prognosis. Patients with p161NK4A negative tumours had a significantly shorter survival (4 months) than those with p16INK41 protein expression (15 months, p=0.0001). Furthermore, the loss of p16INK4A protein expression correlated strongly with the pressure of distant and advanced lymph-node metastases. The best survival was seen in a subgroup of 20 patients with positive p16INK4A expression and intact BAX (p=0.0002). The results of the present study suggest that the loss of BAX and p16INK4A expression are independent markers for poor prognosis in nonsmall cell lung cancer. The study suggests that multimarker analysis of genes involved in apoptosis may be useful for determining individual therapy and for identifying targets for gene-replacement therapy. This should be assessed in a prospective study with a larger cohort of patients.

Gene transfer into solid tumours--is a special application device beneficial?

The replacement of inactivated tumour suppressor genes is a promising approach in cancer therapy. The aim of this study was to evaluate the influence of technical determinants on the efficiency of adenoviral-mediated gene transfer into solid tumours. Therefore, we compared the efficacy of two different injection needle types, a conventional needle and a modified needle characterised by perforations at the side of the shaft in vivo. The total amount of adenoviral vector DNA and the activity of the transferred reporter gene were quantitatively analysed by polymerase chain reaction (PCR) specific for the E4 region of the Ad vector genome and the beta-galactosidase assay, respectively. The levels of adenoviral DNA, as well as the total beta-galactosidase activity, varied widely, but were not significantly different for the two groups. These results suggest, that the efficiency of intratumoral gene transfer cannot be improved by the design of the application device.

Endotracheal balloon dilatation and stent implantation in benign stenoses.

BACKGROUND: Tracheal reconstruction is the treatment of choice in nontumorous tracheal stenoses, but recurrences and concomitant medical conditions limit this approach. We investigated the outcome after balloon dilatation and silicone stent implantation. METHODS: Forty-two patients with inoperable tracheal stenoses underwent balloon dilatation and afterward silicone stent implantation. Patients were divided into two groups, in group A 24 patients received tracheal stents as a temporary treatment. In group B, definitive stenting was done in 18 patients with severe concomitant medical conditions that did not allow for stent removal. RESULTS: Immediate results were satisfactory in all patients. In group A, stents could be removed in 12 patients after a mean interval of 20 months. Restenting was not required during the following 18.9 months. Twelve patients are still waiting for stent removal after a mean follow-up of 20 months. In group B, mean follow-up is now 48.4 months. Complications included retained secretions, dislocation, and granuloma formation. CONCLUSIONS: Stenting after balloon dilatation is safe and effective in benign tracheal stenoses. After temporary use, stents can be removed when local and general conditions permit. In all other patients, stenting proved beneficial for 5 years as more definitive treatment.

Interventional pneumology in pulmonary bleeding; a review: from the bronchus to the vessel.

Interventional pneumology includes both bronchological and vascular methods of diagnosis and therapy, especially in emergency situations such as pulmonary hemorrhage. In massive pulmonary hemorrhage bronchological diagnosis is required to determine the site and extent of bleeding, as well as angiography of bronchial arteries, and of pulmonary arteries. Bronchus occlusion by aid of balloon catheter or double lumen tube are holding measures until definitive surgery or embolization of bronchial or pulmonary arteries can be performed. The paper suggests a close relationship between bronchoscopic and angiographic diagnosis and therapy in case of severe pulmonary bleeding.

Expression of adhesion molecules in peripheral pulmonary vessels from smokers and nonsmokers.

INTRODUCTION AND RATIONALE: An accumulation of intraalveolar cells, especially of macrophages and granulocytes, can be observed in smokers. Since adhesion molecules are involved in the process of cell accumulation, in this study we investigated the hypothesis that the expression of endothelial adhesion molecules on pulmonary vascular endothelial cells is different in smokers and nonsmokers. METHODS: We investigated lung biopsies from 26 patients who underwent thoracic surgery for localized malignancies (smokers: 15; nonsmokers: 11). Cryostat sections were stained by using immunohistochemistry (APAAP method) with antibodies against E- and P-selectin, the vascular adhesion molecule-1 (VCAM-1), and the intercellular adhesion molecule-1 (ICAM-1). The number of adhesion molecule-positive stained vessels was compared to the total number of vessels identified by the expression of von Willebrand's factor (vWF) and anti-CD31. RESULTS: The two groups investigated showed no differences in the expression of E-, and P-selectin and of VCAM-1. In contrast, the expression of ICAM-1 was significantly increased in smokers (median 25 vessels/section, CI95%: 19-31) compared to nonsmokers (median 16 vessels/section, CI95%: 9-21) (p = 0.030). In smoking subjects, we were also able to demonstrate a positive correlation between the duration of smoking expressed as pack years and the expression of ICAM-1 on pulmonary vessels (Spearman rank coefficient of correlation 0.857; p = 0.0002). CONCLUSION: The observed increased expression of ICAM-1 on pulmonary vascular endothelial cells in smokers compared to nonsmokers may be involved in the increased recruitment of inflammatory cells to the alveolar space of smokers.