Tumor and peritumoral adipose tissue crosstalk: De-differentiated adipocytes influence spread of colon carcinoma cells.

Colorectal cancer is the second leading cause of cancer and often has a fatal course. There are many studies in the literature that have described a close functional relationship between the tumor mass and surrounding tissue, or tumor stroma, which is affected by the continuous metabolic exchange that occurs at the interface between tumor and tissues in contact with it. There is much evidence that the presence of adipose tissue in stroma plays a fundamental role in modulating the tumor microenvironment and promote tumor development, growth, and angiogenesis due to its endocrine characteristics. In this analysis, we have studied the alterations of adipose tissue surrounding colorectal tumors with MRI and optical imaging in vivo techniques to monitor tumor progression and also performed histological and molecular analysis. We detected differences in the principal adipose markers expressed by adipocytes residing around the rectal colon and observed that peritumoral adipose tissue is exposed to a mesenchymal transition process that leads to the acquisition of a less differentiated phenotype of adipocyte that represents the main cellular type present in tumor stroma. The mesenchymal transition correlated with the acquisition of more aggressive tumor phenotype and could represent a valid target for tumor therapy.

Luminescence and fluorescence of essential oils. Fluorescence imaging in vivo of wild chamomile oil.

Essential oils are currently of great importance to pharmaceutical companies, cosmetics producers and manufacturers of veterinary products. They are found in perfumes, creams, bath products, and household cleaning substances, and are used for flavouring food and drinks. It is well known that some of them act on the respiratory apparatus. The increasing interest in optical imaging techniques and the development of related technologies have made possible the investigation of the optical properties of several compounds. Luminescent properties of essential oils have not been extensively investigated. We evaluated the luminescent and fluorescent emissions of several essential oils, in order to detect them in living organisms by exploiting their optical properties. Some fluorescent emission data were high enough to be detected in dermal treatments. Consequently, we demonstrated how the fluorescent signal can be monitored for at least three hours on the skin of living mice treated with wild chamomile oil. The results encourage development of this technique to investigate the properties of drugs and cosmetics containing essential oils.

A new model of rectal cancer with regional lymph node metastasis allowing in vivo evaluation by imaging biomarkers.

OBJECT: The work is aimed to develop a murine model of rectal cancer, which could be used to monitor lymph node metastasis development by magnetic resonance imaging (MRI) and optical imaging (OI) techniques. SUBJECTS AND METHODS: Ht-29 cancer cells were directly injected into the submucosal layer of the rectum of athymic nude mice using trans-anal rectal cancer cell injection (TARCI). Thirty-six mice were inoculated with 10×10(5) cells and five mice were treated with sterile phosphate buffer solution. One to 4 weeks after cell injection, tumor growth was evaluated in vivo using T2-weighted MRI at 4.7T. A further group of animal (n=6) treated with ht-29_luc cells, with the same protocol, was monitored by optical imaging. In both groups, the presence of the primary tumor and of lymph nodes metastasis was confirmed by histology. RESULTS: In all animals, primary tumors were detectable by MRI, 1 week from TARCI. After 4 weeks primary tumors showed a mean longitudinal diameter of about 2cm. All animals developed regional lymph node metastases. Others organs (e.g. lung or liver) were not affected. In fat-suppressed, T2-weighted MRI, lymph nodes appeared as small areas characterized by hyper-intense signal compared to muscle. OI permitted evaluation of the primary tumor growth in perineal region. CONCLUSIONS: TARCI of ht-29 cells into the rectum of nude mice is a feasible way to obtain a easily reproducible model of regional lymph node metastases could be monitored by magnetic resonance and optical imaging techniques.

Inhibition of tyrosine kinase receptors by SU6668 promotes abnormal stromal development at the periphery of carcinomas.

Dynamic contrast-enhanced (albumin-Gd-DTPA) magnetic resonance imaging, performed during 2 weeks of daily administration of an inhibitor of tyrosine kinase receptors (SU6668) in an HT-29 colon carcinoma model, revealed the onset of a hyper-enhancing rim, not observed in untreated tumours. To account for tissue heterogeneity in the quantitative analysis, we segmented tumours into three subunits automatically identified by cluster analysis of the enhancement curves using a k-means algorithm. Transendothelial permeability (Kps) and fractional plasma volume (fPV) were calculated in each subunit. An avascular and necrotic region, an intermediate zone and a well-vascularised periphery were reliably identified. During untreated tumour growth, the identified sub-regions did not substantially change their enhancement pattern. Treatment with SU6668 induced major changes at tumour periphery where a significant increase of Kps and fPV was observed with respect to control tumours. Histology revealed a sub-capsular layer composed of hyper-dense viable tumour cells in the periphery of untreated tumours. The rim of viable neoplastic cells was reduced in treated tumours, and replaced by loose connective tissue characterised by numerous vessels, which explains the observed hyper-enhancement. The present data show a peripheral abnormal development of cancer-associated stroma, indicative of an adaptive response to anti-angiogenic treatment.

US, colour-Doppler US and fine-needle aspiration biopsy in the diagnosis of thyroid nodules.

PURPOSE: The purpose of this study was to correlate the diagnosis of benign or malignant thyroid nodules obtained with grey-scale ultrasound (US) and colour-Doppler US with the cytological findings after US-guided fine-needle aspiration (FNA). MATERIALS AND METHODS: Between January 2004 and June 2005, 516 thyroid nodules in 420 patients (181 solitary thyroid nodules and 239 multiple nodules) were prospectively evaluated with US, colour-Doppler US and US-guided FNA. The nodules were classified as sonographically benign, suspicious or malignant in accordance with established US criteria. Cytological findings were classified as inadequate, benign, indeterminate, suspicious or malignant. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of US and colour-Doppler US were evaluated using FNA as the reference procedure. RESULTS: The sensitivity, specificity, PPV, NPV and overall accuracy values of grey-scale US were 46%, 73%, 34%, 82% and 67%, respectively, for solitary thyroid nodules and 35%, 72%, 14%, 90% and 68%, respectively, for multiple nodules. The evaluation of nodule vascularity with colour-Doppler US produced a slight increase in sensitivity but a slight reduction in specificity. CONCLUSIONS: Thyroid nodules cannot be accurately characterised using grey-scale US or colour-Doppler US.

Structural and functional MRI following 4-aminopyridine-induced seizures: a comparative imaging and anatomical study.

Structural and functional MRI was used in conjunction with computerized electron microscopy morphometry to study changes 2 h, 24 h and 3 days after 4-aminopyridine-induced seizures lasting 2 h in rats. T2 (relaxation time) values showed changes throughout the cerebral cortex, hippocampus, amygdala and medial thalamus, with a different temporal progression, showing a complete recovery only after 3 days. Two hours after seizures, the apparent diffusion coefficient was decreased throughout the brain compared to control animals, and a further decrease was evident 24 h after seizures. This was followed by a complete recovery at 3 days post-seizures. Functional MRI was performed using regional cerebral blood volume (rCBV) maps. The rCBV was increased shortly after convulsions (2 h) in all structures investigated, with a significant return to baseline values in the parietal cortex and hippocampus, but not in the medial thalamic nuclei, 24 h after seizure onset. No rCBV alterations were detected 3 days after seizures. Electron microscopy of tissue samples of parietal neocortex and hippocampus revealed prominent astrocytic swelling 2 h post-convulsions which decreased thereafter gradually. In conclusion, this experiment reports for the first time structural and functional brain alterations, lasting several hours, in 4-aminopyridine-treated rats after seizure onset. MRI approach combined with histological and ultrastructural analysis provided a clarification of the mechanisms involved in the brain acute response to ictal activity.

Rotational angiography of the carotid artery bifurcation: technical aspects and preliminary results.

PURPOSE: Rotational Angiography (RA), a new modality for performing conventional catheter angiography, enables an accurate evaluation of the artery to be obtained from different points of view by means of the contemporary rotation of the X-ray tube and image intensifier during intrarterial selective injection of contrast media. This paper describes the examination technique and compares the diagnostic accuracy of the RA oblique projections with the data obtained in the antero-posterior (AP) and latero-lateral (LL) projections in the study of the carotid bifurcation. MATERIALS AND METHODS: Thirty patients underwent RA of the supra-aortic vessels to evaluate the degree of a stenosis at the carotid bifurcation suspected at color Doppler imaging. The angiographic examinations were performed on a Philips Integris Allura system able to rotate the arc at a speed of 55 degrees /s with selective catheterisation of both common carotid arteries. RESULTS: The frame showing the greatest degree of stenosis was compared with the frames obtained in the AP and LL projections. 57/60 carotid bifurcations were assessable (3 cases of internal carotid arteries were obstructed). The degree of stenosis evaluated on the most significant of the oblique projections was superior to that shown in the AP and LL projections for 16/30 cases on the right side and for 14/27 cases on the left side. In 4/57 cases (7%) the degree of stenosis was modified from less than 70% to more than 70%. No adverse event was observed due to catheterisation. CONCLUSIONS: RA enables the complete three-dimensional evaluation of the carotid bifurcation, and generally yields more accurate information on the degree of the stenosis in comparison with AP and LL technique. The study was successfully carried out in all cases, however slightly longer examination times due to the setup requirements of the system. This was largely compensated by the quality of the information yielded, which required no additional projections to be performed. Moreover, the high frame rate of 25 frames per second showed the haemodynamic flow through the lesion.