The Angiopoietin/Tie2 Axis Mediates Malignant Pleural Effusion Formation

Purpose

Angiopoietins and their receptor, Tie2, participate in angiogenesis, regulation of vascular permeability, and inflammation, all central to the pathogenesis of malignant pleural effusions (MPEs). In the present study, we aimed to examine the role of the angiopoietin/Tie2 axis in MPE pathogenesis.

Experimental Design

MPE was induced by intrapleural injection of murine adenocarcinoma cells in C57BL/6 mice. Animals were given twice-weekly intraperitoneal injections of 40 mg/kg MuTekdeltaFc or vehicle. MuTekdeltaFc is a soluble Tie2 (sTie2) receptor that binds murine angiopoietins thereby disrupting their interaction with Tie2 receptors expressed on tissues. Animals were killed on day 14.

Results

Angiopoietin/Tie2 axis blockade significantly reduced pleural fluid volume and pleural tumor foci. The mean ± SEM pleural fluid volumes were 617 ± 48 µl and 316 ± 62 µl for the control and treated groups, respectively (P = .001), whereas the mean ± SEM tumor foci were 7.3 ± 1.0 and 3.0 ± 0.52 for the control and treated groups, respectively (P = .001). In addition, tumor-associated cachexia, tumor angiogenesis, pleural vascular permeability, recruitment of inflammatory cells to the pleural cavity, and local elaboration of vascular endothelial growth factor and interleukin 6 were also downregulated, and tumor cell apoptosis was induced in animals treated with the inhibitor.

Conclusions

Our results indicate that the angiopoietin/Tie2 axis is an important component of MPE pathogenesis. Further studies are required to determine whether therapeutic interventions targeting this pathway could be beneficial for patients with MPE.     

Hypopharyngeal perforation because of blunt neck trauma

Hypopharyngeal rupture because of blunt neck trauma is an extremely rare clinical entity. Early diagnosis and appropriate management are of great importance, given that an overlooked injury can lead to catastrophic consequences. We herein describe the case of a 21-year-old man who presented with a knee injury after a low-speed motor cycle accident, but was otherwise asymptomatic. A detailed history was taken, whereas thorough clinical examination revealed slight tenderness of the anterior neck. Complete imaging examinations finally revealed characteristic findings of hypopharyngeal perforation. The patient was treated conservatively with success. A high degree of clinical suspicion is therefore the key to an early diagnosis and successful management of this rare injury.     

Lifestyle factors and serum androgens among 636 middle aged men from seven countries in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Objective  To evaluate the association between lifestyle and dietary factors and serum concentrations of androgens in middle-aged healthy men. Methods  We conducted a cross-sectional analysis of the association of lifestyle factors with circulating concentrations of androstenedione (A-dione), 3-α-androstanediol glucuronide (A-diol-g), testosterone (T), SHBG (sex hormone-binding globulin), and free testosterone (FT) among 636 men in the European Prospective Investigation into Cancer and Nutrition. Results  Compared with the youngest age group (40–49 years), the oldest (70–79 years) had a higher mean concentration of SHBG (by 44%) and lower mean concentrations of A-diol-g (by 29%) FT (19%). Men in the highest BMI group (≥29.83 kg/m²) had a higher mean A-diol-g concentration (by 38%) and lower mean concentration of T (by 20%) SHBG (29%) compared with the lowest (<24.16 kg/m²). Current smokers had higher mean concentrations of T (by 13%), SHBG (14%), and A-dione (15%) compared with never smokers. Physical activity and dietary factors were not associated with androgen concentrations, although men in the highest fifth of alcohol intake had higher mean concentrations of A-dione (by 9%), FT (11%) compared with the lowest. Conclusion  Our results suggest that age, body weight, smoking, and alcohol intake are associated with circulating androgen concentrations in men.     

Expression of integrin-linked kinase and its binding partners in chondrosarcoma: association with prognostic significance

Integrin-linked kinase (ILK) and its binding partners alpha-parvin, beta-parvin, Mig-2 and Migfilin are important components of the cell-matrix adhesions implicated in cell motility, growth, survival and ultimately carcinogenesis. Herein, we investigated immunohistochemically the expression of these molecules in cartilaginous neoplasms and explored their involvement in chondrosarcoma pathobiology and behaviour. Our analyses revealed that ILK, alpha-parvin, beta-parvin and Mig-2 are expressed in the majority of chondrosarcomas but in a small proportion of enchondromas, implying that these proteins might have a role in the development and progression of chondrogenic neoplasms. Moreover, our findings highlight the possibilities that ILK might serve as biological marker that could accurately predict a high-grade tumour and that Mig-2 may function as a promising prognostic indicator of high-risk patients.