Linear Accelerator Test Facility at LNF Conceptual Design Report

Test beam and irradiation facilities are the key enabling infrastructures for research in high energy physics (HEP) and astro-particles. In the last 11 years the Beam-Test Facility (BTF) of the DA{\Phi}NE accelerator complex in the Frascati laboratory has gained an important role in the European infrastructures devoted to the development and testing of particle detectors. At the same time the BTF operation has been largely shadowed, in terms of resources, by the running of the DA{\Phi}NE electron-positron collider. The present proposal is aimed at improving the present performance of the facility from two different points of view: extending the range of application for the LINAC beam extracted to the BTF lines, in particular in the (in some sense opposite) directions of hosting fundamental physics and providing electron irradiation also for industrial users; extending the life of the LINAC beyond or independently from its use as injector of the DA{\Phi}NE collider, as it is also a key element of the electron/positron beam facility. The main lines of these two developments can be identified as: consolidation of the LINAC infrastructure, in order to guarantee a stable operation in the longer term; upgrade of the LINAC energy, in order to increase the facility capability (especially for the almost unique extracted positron beam); doubling of the BTF beam-lines, in order to cope with the signicant increase of users due to the much wider range of applications.Comment: 71 page

Thyroid Cancer Imaging In Vivo by Targeting the Anti-Apoptotic Molecule Galectin-3

Background The prevalence of thyroid nodules increases with age, average 4-7% for the U.S.A. adult population, but it is much higher (19-67%) when sub-clinical nodules are considered. About 90% of these lesions are benign and a reliable approach to their preoperative characterization is necessary. Unfortunately conventional thyroid scintigraphy does not allow the distinction among benign and malignant thyroid proliferations but it provides only functional information (cold or hot nodules). The expression of the anti-apoptotic molecule galectin-3 is restricted to cancer cells and this feature has potential diagnostic and therapeutic implications. We show here the possibility to obtain thyroid cancer imaging in vivo by targeting galectin-3. Methods The galectin-3 based thyroid immuno-scintigraphy uses as radiotracer a specific 99mTc-radiolabeled mAb. A position-sensitive high-resolution mini-gamma camera was used as imaging capture device. Human galectin-3 positive thyroid cancer xenografts (ARO) and galectin-3 knockout tumors were used as targets in different experiments in vivo. 38 mice with tumor mass of about 1 gm were injected in the tail vein with 100 ?Ci of 99mTc-labeled mAb to galectin-3 (30 ?g protein/in 100 ?l saline solution). Tumor images were acquired at 1 hr, 3 hrs, 6 hrs, 9 hrs and 24 hrs post injection by using the mini-gamma camera. Findings Results from different consecutive experiments show an optimal visualization of thyroid cancer xenografts between 6 and 9 hours from injection of the radiotracer. Galectin-3 negative tumors were not detected at all. At 6 hrs post-injection galectin-3 expressing tumors were correctly visualized, while the whole-body activity had essentially cleared. Conclusions These results demonstrate the possibility to distinguish preoperatively benign from malignant thyroid nodules by using a specific galectin-3 radio-immunotargeting. In vivo imaging of thyroid cancer may allow a better selection of patients referred to surgery. The possibility to apply this method for imaging and treatment of other galectin-3 expressing tumors is also discussed

The Loss of the p53 Activator HIPK2 Is Responsible for Galectin-3 Overexpression in Well Differentiated Thyroid Carcinomas

Background: Galectin-3 (Gal-3) is an anti-apoptotic molecule involved in thyroid cells transformation. It is specifically overexpressed in thyroid tumour cells and is currently used as a preoperative diagnostic marker of thyroid malignancy. Gal-3 expression is downregulated by wt-p53 at the transcriptional level. In well-differentiated thyroid carcinomas (WDTCs) there is an unexplained paradoxical concomitant expression of Gal-3 and wt-p53. HIPK2 is a co-regulator of different transcription factors, and modulates basic cellular processes mainly through the activation of wt-p53. Since we demonstrated that HIPK2 is involved in p53-mediated Gal-3 downregulation, we asked whether HIPK2 deficiency might be responsible for such paradoxical Gal-3 overexpression in WDTC. Methodology/Principal Findings: We analyzed HIPK2 protein and mRNA levels, as well as loss of heterozygosity (LOH) at the HIPK2 locus (7q32-34), in thyroid tissue samples. HIPK2 protein levels were high in all follicular hyperplasias (FHs) analyzed. Conversely, HIPK2 was undetectable in 91.7% of papillary thyroid carcinomas (PTCs) and in 60.0% of follicular thyroid carcinomas (FTCs). HIPK2 mRNA levels were upregulated in FH compared to normal thyroid tissue (NTT), while PTC showed mean HIPK2 mRNA levels lower than FH and, in 61.5% of cases, also lower than NTT. We found LOH at HIPK-2 gene locus in 37.5% of PTCs, 14.3% of FTCs and 18.2% of follicular adenomas. To causally link these data with Gal-3 upregulation, we performed in vitro experiments, using the PTC-derived K1 cells, in which HIPK2 expression was manipulated by RNA interference (RNAi) or plasmid-mediated overexpression. HIPK2 RNAi was associated with Gal-3 upregulation, while HIPK2 overexpression with Gal-3 downregulation. Conclusions/Significance: Our results indicate that HIPK2 expression and function are impaired in WDTCs, in particular in PTCs, and that this event explains Gal-3 overexpression typically observed in these types of tumours. Therefore, HIPK2 can be considered as a new tumour suppressor gene for thyroid cancers

BETA2-MICROGLOBULIN SERUM LEVEL IS NOT A MARKER OF DISEASE ACTIVITY IN MULTIPLE SCLEROSIS

Beta2-microglobulin (beta2-MG) is a pharmacodynamic marker of interferon-beta activity in multiple sclerosis (MS). Its role in the natural course of the disease is not fully known. We analyzed the spontaneous fluctuation of beta2-MG in free-treatment MS patients during a short-time course to quantify beta2-MG as a marker of disease activity/progression. Thirty MS patients were clinically assessed and imaged monthly over a 3-month period. Sera were collected concomitantly for the evaluation of beta2-MG, by means of an enzyme-linked immunosorbent assay. Sera from 20 healthy individuals (HI) were drawn and used as controls. The Mann-Whitney test was used when appropriate and time effect on radiological and biological measures was assessed by means of the random effect models. Eight (26.7%) patients experienced a clinical relapse but three (10%) required steroid treatment. A reduction in the contrast-enhancing lesion load (P = 0.02) and a trend (P = 0.07) toward a decrease in brain parenchyma fraction were observed. Baseline levels of beta2-MG were similar in patients and HI. Patients' beta2-MG values increased over the 3-month time period (P = 0.05) but did not exceed those detected in HI at any time point. These results failed to demonstrate the validity of beta2-MG as a surrogate marker of disease in MS