Recursive Partitioning Analysis of Mediastinal N2 Lymph Node Involvement with Selected Biological Markers in Operable Non-small Cell Lung Cancer: A Correlative Study

Background: Expressions of various biomarkers in non-small cell lung cancer (NSCLC) have been linked with the prognosis and involvement of mediastinal lymph nodes.Methods: In this study, we utilized recursive partitioning analysis (RPA) by using P53, c-erb-B2, and P-glycoprotein (PGP) expressions evaluated by immunohistochemistry to estimate retrospectively the likelihood of the occult N2 mediastinal lymph node involvement in patients with operable NSCLC.Results: In univariate tests, immunohistochemical staining of the primary tumor for these 3 markers in 61 patients undergoing surgery revealed no direct relationship with the N2 involvement. However, RPA demonstrated in patients aged 75 and with 4 mediastinal lymph nodes removed that, high PGP expression frequency (20%) predicted an increased likelihood of the N2 involvement (46.7%, R2 = 0.25). Univariate nominal logistic regression analysis revealed that RPA group affiliation, and the number of mediastinal lymph nodes resected (logarithmic transformation) were associated with the metastasis to N2 lymph nodes (χ2 = 17.59, p = 0.0005, and χ2 = 2.40, p = 0.0654, respectively). Multivariate analysis confirmed that only RPA group affiliation predicted the N2 involvement (χ2 = 14.63, p = 0.0022).Conclusion: This study shows for the first time that PGP expression of the primary tumor may help to predict the occult N2 mediastinal lymph node involvement in NSCLC. Thus, further research is required to understand whether PGP expression may aid in the decision process for preoperative mediastinoscopy

Differential expression of VASP in normal lung tissue and lung adenocarcinomas

Background: Vasodilator stimulated phosphoprotein (VASP) is associated with focal adhesions and is thought to have an important role in actin filament assembly and cell motility. We hypothesise that an increase in the expression of VASP is involved in the progression and invasion of lung adenocarcinomas in parallel to tumour progression. A study was undertaken to analyse VASP expression in normal lung tissue and lung adenocarcinomas. Methods: Human lung tissues with adenocarcinomas (n = 26) were used. Normal lung tissue specimens (n = 14) were taken from areas a standard distance (3 cm) from resected adenocarcinomas of patients who underwent surgical lung resection. Adenocarcinomas were classified according to pathological staging and histopathological grades. Tissues were stained for VASP using immunohistochemistry. Results: Normal lung pneumocytes showed no VASP expression while alveolar macrophages had the strongest immunoreactivity for VASP. Bronchial epithelium (surface epithelium, goblet cells) and bronchial gland cells had a very weak immunoreactivity for VASP. Adenocarcinomas had significantly greater VASP expression than normal epithelium (p<0.001). Moreover, VASP expression in adenocarcinomas increased significantly with more advanced tumour stage (p<0.001). Conclusions: The spatial and differential expression of VASP in normal lung tissue and lung adenocarcinomas suggests that it is likely to be involved in the differentiation of normal lung cells to adenocarcinomas. The significant increase in the expression of VASP in adenocarcinomas in parallel to pathological staging suggests that it may regulate the invasive behaviour of lung adenocarcinomas as adenocarcinoma invasion is increased in more advanced tumours

Effect of a Cholesterol Rich Diet, Recurrent Infection and Possible Treatment Modalities on the Pulmonary Vascular System: An Experimental Study

Objective: Infection may lead to inflammation, atherosclerosis and thrombotic vascular events. The atherosclerotic effect of hypercholesterolaemia on the vascular system is well-known. However, limited studies were done on the therapeutic and preventative agents. The aim of this study was to investigate the effects of infection and cholesterol rich diet combined with an antibiotic, anti-inflammatory agent and red wine on the pulmonary vascular system. Methods: Fifty-nine rats were evaluated. Six groups were created: Control-Group I (n = 10); infection – Group II (n = 9), infection-cholesterol rich diet – Group III (n = 12), infection-cholesterol rich diet-cefepime – Group IV (n = 11); infection-cholesterol rich diet-diclofenac potassium – Group V (n = 9); infection-cholesterol rich diet and red wine – Group VI (n = 8). Blood samples of rats were collected for cholesterol analysis every month. Sections of central pulmonary arteries were examined for thickness of the intima and medial wall by computerised image analysis. Results: There was a statistically significant difference in serum cholesterol levels and in thickness of the intima between the groups (p = 0.000). The rest of the groups had more intimal thickening than Group I (p = 0.000). Group III had thicker intima than Groups IV and V (p = 0.009, p = 0.011 respectively). There was no significant difference between the groups in thickness of media (p = 0.432). Conclusion: Infection and cholesterol rich diet have a synergistic effect on atherosclerosis in pulmonary arteries. However, antibiotics and anti-inflammatory agents could be useful in prevention. Key Words: Atherosclerosis, cefepime, diclofenac potassium, pulmonary artery, red wine "Efecto de la dieta Rica en Colesterol, la Infección Recurrente, y las Posibles Modalidades de Tratamiento Sobre el Sistema Vascular Pulmonar: un Estudio Experimental" RESUMEN Objetivo: La infección puede conducir a inflamación, ateroesclerosis y eventos vasculares trombóticos. El efecto aterosclerótico de la hipercolesterolemia en el sistema vascular es bien conocido. Sin embargo, se hicieron estudios limitados sobre los agentes preventivos y terapéuticos. El objetivo de este estudio fue investigar los efectos de la infección y la dieta rica en colesterol, combinados con agentes antibióticos, anti-inflamatorios, y vino tinto, sobre el sistema vascular pulmonar. Métodos: Cincuenta y nueve ratas fueron evaluadas. Se hicieron seis grupos: grupo-control I (n = 10), grupo-infección II (n = 9), grupo infección-dieta rica en colesterol III (n = 12), grupo-infección-dieta rica en colesterol-cefepima IV (n = 11), grupo-infección-dieta rica en colesterol-diclofenaco potásico V (n = 9), grupo-infección-dieta rica en –vino tinto VI (n = 8). Se tomaron muestras de sangre de ratas para analizar el colesterol cada mes. Se examinaron secciones de las arterias pulmonares centrales para determinar el grosor de la pared íntima y media mediante análisis computarizado de imágenes. Resultados: Hubo una diferencia estadísticamente significativa en los niveles de colesterol en suero y el grosor de la íntima entre los grupos (p = 0.000). El resto de los grupos tenía más engrosamiento de la íntima que el grupo I (p = 0.000). El grupo III tenía una íntima más gruesa que los grupos IV y V (p = 0,009, p = 0.011 respectivamente). No hubo ninguna diferencia significativa entre los grupos en cuanto al espesor de la media (p = 0.432). Conclusión: La infección y la dieta rica en colesterol tienen un efecto sinérgico sobre la aterosclerosis en las arterias pulmonares. Sin embargo, los antibióticos y los agentes antiinflamatorios podrían ser útiles para la prevención. Palabras claves: Aterosclerosis, cefepima, diclofenaco potásico, arteria pulmonar, vino tinto