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Esposito C.,CNR Institute of Neuroscience | Esposito C.,University of Naples Federico II | Marasco D.,CNR Institute of Neuroscience | Marasco D.,University of Naples Federico II | And 3 more authors.
Biochemical and Biophysical Research Communications | Year: 2011

HBHA is a mycobacterial cell surface protein that mediates adhesion to epithelial cells and that has been implicated in the dissemination of Mycobacterium tuberculosis (Mtb) from the site of primary infection. In this work, we demonstrate that HBHA is able to bind G-actin whereas its shorter form, deprived of the lysine-rich C-terminal region (HBHAΔC), does not bind. Consistently, interaction of actin with HBHA is competitive with heparin binding. Notably, we also observe that HBHA, but not HBHAΔC, clearly hampers G-actin polymerisation into F-actin filaments. Since Mtb escapes from the phagosome into the cytosol of host cells, where it can persist and replicate, HBHA is properly localised on the bacterial surface to regulate the dynamic process of cytoskeleton formation driven by actin polymerisation and depolymerisation. © 2011 Elsevier Inc.

Cellini F.,Policlinico Universitario Campus BioMedico | Valentini V.,Policlinico Universitario Agostino Gemelli
ONCOLOGY (United States) | Year: 2012

The optimal approach to the diagnosis and treatment of locally advanced rectal cancer involves multidisciplinary, integrated management. In the past 30 years, survival and freedom from disease have increased, but the ideal multidisciplinary management remains to be determined. The preferred integrated treatment modality is preoperative radio(chemo)therapy followed by total mesorectal excision. Certain aspects of this standard are still debated, and the European and American approaches vary. The chief recommendations per international guidelines are summarized, and the next generation of integrated treatments for locally advanced rectal cancer is discussed.

Lambin P.,Maastricht University | Van Stiphout R.G.P.M.,Maastricht University | Starmans M.H.W.,Maastricht University | Rios-Velazquez E.,Maastricht University | And 11 more authors.
Nature Reviews Clinical Oncology | Year: 2013

With the emergence of individualized medicine and the increasing amount and complexity of available medical data, a growing need exists for the development of clinical decision-support systems based on prediction models of treatment outcome. In radiation oncology, these models combine both predictive and prognostic data factors from clinical, imaging, molecular and other sources to achieve the highest accuracy to predict tumour response and follow-up event rates. In this Review, we provide an overview of the factors that are correlated with outcome-including survival, recurrence patterns and toxicity-in radiation oncology and discuss the methodology behind the development of prediction models, which is a multistage process. Even after initial development and clinical introduction, a truly useful predictive model will be continuously re-evaluated on different patient datasets from different regions to ensure its population-specific strength. In the future, validated decision-support systems will be fully integrated in the clinic, with data and knowledge being shared in a standardized, instant and global manner. © 2013 Macmillan Publishers Limited. All rights reserved.

Roelofs E.,Maastricht University | Dekker A.,Maastricht University | Meldolesi E.,Policlinico Universitario Agostino Gemelli | Van Stiphout R.G.P.M.,Maastricht University | And 2 more authors.
Radiotherapy and Oncology | Year: 2014

Extensive, multifactorial data sharing is a crucial prerequisite for current and future (radiotherapy) research. However, the cost, time and effort to achieve this are often a roadblock. We present an open-source based data-sharing infrastructure between two radiotherapy departments, allowing seamless exchange of de-identified, automatically translated clinical and biomedical treatment data. © 2013 Elsevier Ireland Ltd. All rights reserved.

Costamagna G.,Policlinico Universitario Agostino Gemelli | Cesaro P.,Policlinico Universitario Agostino Gemelli
Annali Italiani di Chirurgia | Year: 2012

Background: Early Gastric Cancer (EGC) is defined as a neoplasm confined to the mucosa or submucosa regardless of regional lymph node metastasis. The rate of EGC, which varies by country, is up to 40-60% of all gastric cancer cases in Japan, whilst in Western countries, the proportion remains at 5-10%. There is a strong male predominance in EGC. The average 5-year survival rate of patients with EGC reached over 90% in Japanese and European data. Materials and Methods: Many EGC patients present with symptoms suggestive of a benign gastric ulcers. The combination of serum pepsinogen and Helicobacter pylori status may provide even more sensitive information for screening. However high-quality endoscopic evaluation with biopsy is the key to diagnosis. To improve the quality of observation several endoscopic imaging modalities have been developed for the diagnosis of early gastric cancer. Endoscopic resection is a viable alternative to surgery for curative treatment of EGC, with similar long term results. Endoscopic mucosal resection (EMR) of EGC without any risk of lymph node metastasis was developed in Japan in the 1980s, and it has been one of the standard treatments of EGC for nearly 20 years. Recently, several EMR techniques developed in Japan have been accepted and done in Western countries. These EMR techniques are safe and efficacious but unsuitable for large lesions. Discussion: Because we could not remove a large lesion in 1 fragment, which was very important for the precise diagnosis of tumor depth, local recurrence increased in large-lesion cases. An innovative procedure using newly developed endoscopic knives, called endoscopic submucosal dissection (ESD), was developed in the late 1990s, which made it possible to remove a large lesion en bloc. Conclusion: Theoretically, ESD has no limitation with respect to tumor size; therefore, it is expected to replace the surgical treatment in some situations. Although ESD has spread throughout Japan within a short period, there remain several disadvantages, such as a higher incidence of complications and a requirement of higher endoscopic skills compared to those of conventional EMR methods.

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