CONJUGATED BRANCHED PEPTIDES AS TARGETING AGENTS FOR TUMOR IMAGING AND THERAPY

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CONJUGATED BRANCHED PEPTIDES AS TARGETING AGENTS FOR TUMOR IMAGING AND THERAPY

Membrane receptors for endogenous peptides like Somatostatin, Neurotensin, Bombesin and many others, are over-expressed in different human cancers and might be targeted as tumor-specific antigens. Efficiency of peptide-receptor targeting depends on the presence and concentration of receptors on neoplastic tissues. Our goal is producing peptide molecules that can be used for both a specific receptor-tracing test and for therapy or in vivo imaging, by delivering radio or chemotherapeutic moieties to the same receptors on tumor cells. We previously demonstrated that peptides synthesized in a branched form known as as Multiple Antigen Peptides (MAP) can retain biological activity and become extremely resistant to endogenous proteases and peptidases (1). An important possible development of protease-resistant MAPs, is the application to tumor therapy and in vivo imaging. Analogues of neurotensin (NT) and its functional fragment NT(8- 13) are under investigation to target a variety of human tumors overexpressing NT receptors. We demonstrated that the tetra-branched MAP form of NT and NT(8-13), fully retain their biological activity and become much more resistant to proteases (1). NT oligo-branched peptides are therefore candidates for the development of new specific tumor-targeted biomolecules. In the present work, different NT analogues were synthesised as tetra-branched MAPs, where the NT sequences behave as the tumor targeting moiety, while functional units for treatment or tracing are bound at the C-terminus of the molecule. Tetra-branched NT conjugated to fluorophores were synthesized and tested for receptor binding on different human tumor cell lines. Once verified that the conjugation of the branched peptide did not reduce its ability to bind the receptor, we tested our peptides on samples from surgical resection of colon and pancreas adenocarcinoma, in comparison with healthy tissues from the same patients. Confocal images show a general good staining by branched NT peptides in most tumor samples and a much lower staining in healthy tissue from the same patients, indicating a good selectivity of the peptide. The same tetra-branched peptide was conjugated to chemotherapic drugs and tested for cytotoxicity toward tumor cells in vitro and in animal models. Results indicate promising features of branched NT for selective tumor targeting

Relationship between the quantity of nerve exposure during bilateral sagittal split osteotomy surgery and sensitive recovery

The purpose of this study was to evaluate how different exposures of the V3 nerves during orthognathic surgery impact neurosensory disturbances. METHODS: The study included 127 patients who underwent either bilateral sagittal split osteotomy (BSSO) or BSSO with maxillary le Fort 1. They were divided into 6 groups, identified by the quantity of V3 nerve exposure. All patients were examined in a pre-op period and again after 1, 3, 6 months post-op. The standardized tests used were to clarify the objective and subjective neurosensory status of the exposed nerve. Neurosensory evaluation included; a pin prick test, the 2 points discriminator, light touch, warm and cold tests, and blunt discrimination. They were all done bilaterally on the lower lip area. RESULTS: In only 2 patients the nerve was damaged during surgery and thus they were not included in this study. In 10.2% of patients there was no nerve exposure, 25.2% had longitudinal vestibular segment nerve exposed, 22.8% had the longitudinal upper-vestibular segment exposed, 20.5% had the longitudinal lower-vestibular segment exposed, 14.2% had the longitudinal upper-lower-vestibular segment exposed, and in 7.1% of patients the nerve was totally exposed. Given the estimated time of 1 month there was 100% recovery in patients whose nerve was unexposed. Considering the other patients, the authors had a variable number of patients who did not recover completely. CONCLUSION: The authors estimate a correlation between the recovery time and the quantity of the exposed nerve. There is a high incidence of neurosensory disturbance in the lower lip and chin after BSSO and intraoperative quantity of nerve exposure

Central But Not Brachial Blood Pressure Predicts Cardiovascular Events in an Unselected Geriatric Population The ICARe Dicomano Study

ObjectivesThe present study investigated whether central blood pressure (BP) predicts cardiovascular (CV) events better than brachial BP in a cohort of normotensive and untreated hypertensive elderly individuals.BackgroundLimited and conflicting data have been reported on the prognostic relevance of central BP compared with brachial BP.MethodsCommunity-dwelling individuals ≥65 years of age, living in Dicomano, Italy, underwent an extensive clinical assessment in 1995 including echocardiography and carotid ultrasonography and applanation tonometry. In 2003, vital status and CV events were assessed, reviewing the electronic database of the Regional Ministry of Health. Only normotensive (n = 173) and untreated hypertensive subjects (95 diastolic and 130 isolated systolic) were included in the present analysis.ResultsDuring 8 years, 106 deaths, 45 of which were cardiovascular, and 122 CV events occurred. In univariate analyses, both central and brachial systolic blood pressure (SBP) and pulse pressure (PP) predicted CV events (all p < 0.005); however, in multivariate analyses, adjusting for age and gender, higher carotid SBP and PP (hazard ratios 1.19/10 and 1.23/10 mm Hg, respectively; both p < 0.0001) but neither brachial SBP nor PP independently predicted CV events. Similarly, higher carotid SBP but not brachial pressures independently predicted CV mortality (hazard ratio 1.37/10 mm Hg; p < 0.0001).ConclusionsOur prospective study in an unselected geriatric population demonstrates superior prognostic utility of central compared with brachial BP

New Perspectives for Postmortem Human Satellite Cells of Different Embryological Origin

Human postmortem skeletal muscles are a unique source of satellite cells for skeletal muscle regenerative studies. Presomite and somite satellite cells obtained by postmortem muscles have been established as populations of human skeletal muscle precursor cells able to proliferate and differentiate in vitro. It is extremely interesting to have access to a large amount of postmortem human skeletal muscle precursor cells, especially from craniofacial as well as limb skeletal muscles in order to evaluate their potential application not only for the fundamental understanding of muscle physiology and diseases but also for drug testing in a challenging 3D-shaping muscles like skeletal muscle microphysiological systems