Bronchoalveolar Lavage Fluid Characteristics of Patients With Sarcoidosis and Nonsarcoidosis Interstitial Lung Diseases: Ten-Year Experience of a Single Center in Turkey.

BACKGROUND: Bronchoalveolar lavage (BAL) is a noninvasive and useful technique for evaluating interstitial lung diseases (ILDs). Flow cytometric analysis of BAL fluid reveals specific diagnostic information in some unusual ILDs, and helps to narrow down the possible causes of interstitial diseases in most patients with more common disorders. A high BAL CD4/CD8 ratio is highly specific for sarcoidosis but can also be seen in other ILDs. OBJECTIVES: In this retrospective, descriptive, cross-sectional study, we compared BAL fluid characteristics and clinical variables in patients with sarcoidosis and non-sarcoidosis ILDs in a large cohort. PATIENTS AND METHODS: The study was conducted in a tertiary university hospital in Zonguldak, the biggest city of the western Black Sea region of Turkey. Between 2004 and 2014, all patients who underwent both fiberoptic bronchoscopy and BAL with a suspicion of ILD were included in the study, retrospectively. Patients were divided into two main groups: sarcoidosis and non-sarcoidosis ILDs. Non-sarcoidosis ILDs were further divided into subgroups: pneumoconiosis, tuberculosis (TB), collagen vascular diseases, idiopathic interstitial pneumonias, malignancies, and unclassified ILDs. The clinical data of patients, including age, gender, smoking status, pulmonary function tests, and BAL flow cytometric analysis results, were compared among groups. RESULTS: In total, 261 patients (119 sarcoidosis and 142 non-sarcoidosis ILDs) were enrolled. The median (interquartile range) BAL CD4/CD8 ratio and lymphocyte fraction were significantly higher in sarcoidosis than in non-sarcoidosis ILDs: 3.88 (3.76) versus 0.88 (1.01), respectively, and 20.6 (28.3) versus 6.0 (13.7), respectively. T cell receptor γ delta, CD16(+)56(+), CD103(+), CD8(+)103(+), and CD3(+)16(+)56(+) cells were significantly lower in sarcoidosis than in non-sarcoidosis ILDs. The median BAL CD4/CD8 ratios were significantly higher in patients with TB (1.87, P = 0.01) and malignancies (1.69, P = 0.03) than in other non-sarcoidosis ILDs. CONCLUSIONS: Among BAL fluid flow cytometric parameters, CD4/CD8 and lymphocyte fraction may be helpful for distinguishing sarcoidosis from other ILDs, but they are neither specific nor diagnostic for any lung disease. Thus, a multidisciplinary diagnostic discussion is required to differentiate various ILDs.

The influence of cisplatin, doxorubicin, pegylated doxorubicin, oxaliplatin and gemcitabine on mahlavu cell line.

PURPOSE: Hepatocellar carcinoma (HCC) remains a major health problem being the third leading cause of deaths due to cancer worldwide. Because HCC is known to be highly resistant to conventional systemic therapies, single-agent or combination of systemic therapies have been investigated. Today, sorafenib, a multikinase inhibitor, is the only approved systemic agent for the first line treatment of advanced HCC. In this study, we aimed to investigate the influence of different concentrations of cisplatin, doxorubicin, pegylated doxorubicin (PLD), oxaliplatin and gemcitabine by applying these agents either single or in combinations on mahlavu cell line. METHODS: HCC mahlavu cell line was used for the experiments. Cell death was measured by flow cytometry at 48 hrs after incubation with various concentrations (0.1 µg/ml, 1.0 µg/ml and 10 µg/ml) of the drugs. RESULTS: Cell death due to gemcitabine was found to be significantly higher than cell deaths caused by the other single agents including cisplatin, oxaliplatin, doxorubicin and PLD (p<0.001, p<0.001, p<0.001 and p=0.0049, respectively). There was no significant difference between gemcitabine and both the gemcitabine combination with doxorubicin and PLD (p=0.992 and p=0.441, respectively). CONCLUSION: This is a preliminary analysis evaluating the effect of the conventional chemotherapeutic agents on mahlavu cell line in vitro. The findings of this study suggest that gemcitabine-based therapies keep on being the prefered therapeutic approach for the treatment of HCC.

Plasma concentrations of Ang-1, Ang-2 and Tie-2 in gastric cancer.

BACKGROUND/AIM: Ang-1 and Ang-2 have both been identified as ligands for Tie-2, a receptor expressed on endothelial cells (EC). They play critical roles in angiogenesis, in concert with VEGF. Ang-1-binding to Tie-2 maintains and stabilizes mature vessels by promoting interactions between EC and the surrounding extra-cellular matrix. However, Ang-2 shows context-dependent, proangiogenic and antiangiogenic activities. Despite the rapidly accumulating histopathological data reporting differences in the expression of members of the Ang family on the surface of various normal and tumour cells, data for these growth factors in plasma from cancer patients, including gastric cancer, remain scarce. The aims of the present study were to measure the plasma concentrations of Ang-1, Ang-2 and Tie-2 in gastric cancer patients, and to assess the correlation between the concentrations of these factors and the stage of the tumor. PATIENTS AND METHODS: The study cohort consisted of 50 patients (33 male, 17 female) with gastric cancer, ranging in age from 38 to 74 years (mean age 55.3±12.4), and 50 sex- and age-matched, healthy controls. Determinations of Ang-1, Ang-2 and Tie-2 were performed using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Concentrations of Ang-2 and Tie-2 were significantly higher in patients with gastric cancer than controls, while concentrations of Ang-1 were not statistically different between the groups. Concentrations of Ang-1, Ang-2 and Tie-2 were not statistically significantly different in gastric cancer patients with different stages of disease. CONCLUSION: Ang-2 and Tie-2 plasma concentrations might be useful, additional tumor markers in gastric cancer.

Oxidized low-density lipoproteins accumulate in rat lung after experimental lung edema induced by alpha- naphthylthiourea (ANTU).

Oxidation of the low-density lipoprotein (LDL) results in the production of modified LDLs. Oxidation of LDL cholesterol plays a role on the pathogenesis of endothelial dysfunction. This study was designed to investigate the possible participation of the oxidative modification of low density lipoprotein in the lung edema induced by alpha-naphthylthiourea (ANTU), which is a well-known noxious chemical agent on the lung endothelium. When ANTU injected intraperitoneally into rats (15 mg kg(-1)), it produced lung edema as indicated by an increase in lung weight/body weight (LW/BW) ratio and pleural effusion (PE) reaching a maximum within 4 h. A significant lung edema was observed 4 h after intraperitoneally injection of alpha-naphthylthiourea when compared with olive oil-injected control rats. On microscopic examination of alpha-naphthylthiourea-treated rats were shown to have severe lung injury, while no change was observed in olive oil-treated control rats. While there were no staining in control lungs, positive oxidized low-density lipoproteins immune-fluorescent staining were observed in lung edema group. Our study showed that oxidized low-density lipoprotein (oxLDL) accumulated in ANTU-induced lung damage. This is the first study in which accumulation of oxLDL molecules in the intact lung tissue were shown by fluorescent immune-staining method in experimental lung edema. The potential role of oxLDL in this pathology are still under investigation.