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The SDF-1 3'A allelic polymorphism has been reported to influence either positively or negatively the progression of human immunodeficiency virus type 1 (HIV-1) disease. Therefore, the SDF-1 genotype of 729 HIV-1-infected individuals pooled from 3 distinct cohorts was determined. A statistically nonsignificant association between the SDF1-3'A/3'A genotype and accelerated disease progression was evident among seroconverters (n=319), but a striking correlation of decreased survival after either diagnosis of AIDS according to the 1993 definition or loss of CD4(+) T cell counts

Andrea Farini,1,* Chiara Villa,1,* Adrian Manescu,2 Fabrizio Fiori,2 Alessandra Giuliani,2 Paola Razini,1 Clementina Sitzia,1 Giulia Del Fraro,1 Marzia Belicchi,1 Mirella Meregalli,1 Franco Rustichelli,2 Yvan Torrente1 1Stem Cell Laboratory, Department of Neurological Sciences, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico di Milano, Centro Dino Ferrari, Università di Milano, Milano, Italy; 2Università Politecnica delle Marche, Di.S.C.O. - Sezione di Biologia, Biochimica e Fisica Ancona, Italy*These authors contributed equally to this paperAbstract: Recently published reports have described possible cellular therapy approaches to regenerate muscle tissues using arterial route delivery. However, the kinetic of distribution of these migratory stem cells within injected animal muscular dystrophy models is unknown. Using living X-ray computed microtomography, we established that intra-arterially injected stem cells traffic to multiple muscle tissues for several hours until their migration within dystrophic muscles. Injected stem cells express multiple traffic molecules, including VLA-4, LFA-1, CD44, and the chemokine receptor CXCR4, which are likely to direct these cells into dystrophic muscles. In fact, the majority of intra-arterially injected stem cells access the muscle tissues not immediately after the injection, but after several rounds of recirculation. We set up a new, living, 3D-imaging approach, which appears to be an important way to investigate the kinetic of distribution of systemically injected stem cells within dystrophic muscle tissues, thereby providing supportive data for future clinical applications.Keywords: iron nanoparticles, micro-CT, CD133+ stem cells, dystrophic muscles

The recently observed low reproducibility of focus score (FS) assessment at different section depths in a series of single minor salivary gland biopsies highlighted the need for a standardized protocol of extensive histopathological examination of such biopsies in Sjogren's syndrome. For this purpose, a cumulative focus score (cFS) was evaluated on three slides cut at 200-μm intervals from each of a series of 120 salivary biopsies. The cFS was substituted for the baseline FS in the American–European Consensus Group (AECG) criteria set for Sjogren's syndrome classification, and then test specificity and sensitivity were assessed against clinical patient re-evaluation. Test performances of the AECG classification with the original FS and the score obtained after multilevel examination were statistically compared using receiver operating characteristic (ROC) curve analysis. The diagnostic performance of AECG classification significantly improved when the cFS was entered in the AECG classification; the improvement was mostly due to increased specificity in biopsies with a baseline FS ≥ 1 but

After diagnosis of non-functioning pituitary adenoma and impact assessment (pituitary deficiency, visual field disorder), the question of management arises between surgery and surveillance. This part of the Consensus document aims to clarify the principal situations encountered in clinical practice (visual disorder, pituitary deficiency, asymptomatic adenoma, etc.), so as to determine which ones indicate surgery and which ones simple surveillance. Particular contexts are also dealt with (elderly patients, young women hoping for pregnancy, etc). The principal surgical techniques (microscopy, endoscopy, etc.) are also considered. Finally, in case of surgery, the principal pathologic criteria are specified (immunolabeling, proliferation markers, etc.).

The onset of chemo- and/or radio-resistance in tumour cells is one of the main causes of failure of integrated treatment protocols combining intra-arterial administration of platinum derivatives and radiotherapy, and is associated with recurrent disease and/or distant metastases. In the present study, the expression of a series of markers of chemo- and/or radio-resistance was investigated in 21 patients with advanced squamous cell carcinoma of the head and neck treated with combined intra-arterial carboplatin and radiotherapy. The results were correlated with local response to treatment, recurrence and overall and disease-free survival. In non-responders or in patients presenting recurrence, caspase 8 was significantly (p 0.05) under-expressed while p-Gp (p 0.035) and MDR-3 (p 0.049) were significantly over-expressed. Tumours with unfavourable outcome more frequently over-expressed two or more anti-apoptotic factors (p-53, BCL-2, BCL-x) (p 0.01). Patients with shorter overall survival, significantly over-expressed p53 (p 0.04), LRP (p 0.038) and a larger number of trans-membrane transport proteins compared with those who survived more than one year (p 0.013). Finally, patients with the shortest disease-free survival presented over-expression of p53 (p 0.027) and BCL-x (p 0.023). Further studies are necessary to confirm the possibility, in a future perspective, of using a panel of markers of chemo- and radio-resistance to identify those patients potentially sensitive to the treatment and to avoid patients at high risk of resistance from being submitted to ineffective and toxic treatment protocols.

BACKGROUND: Mutations affecting the Capicua transcriptional repressor gene (CIC) on 19q13.2 are frequently associated with a chromosomes 1p and 19q codeletion in oligodendroglial tumors. However, their impact remains poorly understood. EXPERIMENTAL DESIGN: We sequenced the CIC gene on 132 oligodendroglial tumors (109 with 1p19q codeletion), analyzed the patients' outcomes, compared the transcriptomic profile of mutated vs. non mutated tumors, analyzed CIC expression on glioma sections, and transfected the Hs683 cell line with plasmids encoding mutant and wild type CIC. RESULTS: We found 62 (37 truncating and 25 missense) mutations affecting 58/109 codeleted gliomas vs. 1/23 non-codeleted. CIC mutations were associated with a poorer outcome, and a shorter time to anaplastic transformation in grade II codeleted gliomas. Transcriptomic analysis revealed an enrichment of proliferative pathways and oligodendrocyte precursor cell genes' expression profile. Of particular interest are the up-regulation of normally CIC repressed genes such as ETV1, ETV4, ETV5, which promote cell proliferation and invasion, and CCND1 (encoding cyclinD1), suggesting that CIC mutation results in an inactive protein. This hypothesis was further supported by the results of transfecting cells with a truncated form of the protein, resulting in a defect of nuclear addressing, and by the loss of protein expression observed in oligodendrogliomas affected by various mutations. Finally, survival analysis suggested a synergistic effect of CIC mutation and CDKN2A alteration in tumor progression. CONCLUSION: CIC mutations are associated with the activation of proliferative pathways, inhibition of differentiation, and poorer outcome in patients with a 1p19q codeleted gliomas.