Angpt2/Tie2 autostimulatory loop controls tumorigenesis.

Invasive nonfunctioning (NF) pituitary neuroendocrine tumors (PitNETs) are non-resectable neoplasms associated with frequent relapses and significant comorbidities. As the current therapies of NF-PitNETs often fail, new therapeutic targets are needed. The observation that circulating angiopoietin-2 (ANGPT2) is elevated in patients with NF-PitNET and correlates with tumor aggressiveness prompted us to investigate the ANGPT2/TIE2 axis in NF-PitNETs in the GH3 PitNET cell line, primary human NF-PitNET cells, xenografts in zebrafish and mice, and in MENX rats, the only autochthonous NF-PitNET model. We show that PitNET cells express a functional TIE2 receptor and secrete bioactive ANGPT2, which promotes, besides angiogenesis, tumor cell growth in an autocrine and paracrine fashion. ANGPT2 stimulation of TIE2 in tumor cells activates downstream cell proliferation signals, as previously demonstrated in endothelial cells (ECs). Tie2 gene deletion blunts PitNETs growth in xenograft models, and pharmacological inhibition of Angpt2/Tie2 signaling antagonizes PitNETs in primary cell cultures, tumor xenografts in mice, and in MENX rats. Thus, the ANGPT2/TIE2 axis provides an exploitable therapeutic target in NF-PitNETs and possibly in other tumors expressing ANGPT2/TIE2. The ability of tumor cells to coopt angiogenic signals classically viewed as EC-specific expands our view on the microenvironmental cues that are essential for tumor progression.

Effect of radiation dose reduction on texture measures of trabecular bone microstructure: an in vitro study.

Osteoporosis is characterized by bone loss and degradation of bone microstructure leading to fracture particularly in elderly people. Osteoporotic bone degeneration and fracture risk can be assessed by bone mineral density and trabecular bone score from 2D projection dual-energy X-ray absorptiometry images. However, multidetector computed tomography image based quantification of trabecular bone microstructure showed significant improvement in prediction of fracture risk beyond that from bone mineral density and trabecular bone score; however, high radiation exposure limits its use in routine clinical in vivo examinations. Hence, this study investigated reduction of radiation dose and its effects on image quality of thoracic midvertebral specimens. Twenty-four texture features were extracted to quantify the image quality from multidetector computed tomography images of 11 thoracic midvertebral specimens, by means of statistical moments, the gray-level co-occurrence matrix, and the gray-level run-length matrix, and were analyzed by an independent sample t-test to observe differences in image texture with respect to radiation doses of 80, 150, 220, and 500 mAs. The results showed that three features-namely, global variance, energy, and run percentage, were not statistically significant ([Formula: see text]) for low doses with respect to 500 mAs. Hence, it is evident that these three dose-independent features can be used for disease monitoring with a low-dose imaging protocol.