Low doses of 3-aminobenzamide, a poly(ADP-ribose) polymerase inhibitor, stimulate angiogenesis by regulating expression of urokinase type plasminogen activator and matrix metalloprotease 2

Abstract Background: Poly(ADP-Ribose) polymerase (PARP) activity has been demonstrated fundamental in many cellular processes, including DNA repair, cell proliferation and differentiation. In particular, PARP activity has been recently found to affect proliferation, migration, and tube formation of human umbilical vein endothelial cells. In recent times, PARP inhibitors have entered in clinical trials to potentiate cancer treatments by preventing DNA repair, but little is known about the effects performed by different drug concentrations on neoangiogenesis, an essential step in tumor growth. Methods: Human umbilical vein endothelial cells were treated with 3 aminobenzamide (3ABA), a PARP inhibitor, and tested for several different cellular parameters. Results: Here we present in vitro evidence that a low concentration of 3ABA (50 μM), stimulates angiogenesis by decreasing fibrinolytic activity, carried out by urokinase-type plasminogen activator (uPA), and by enhancing matrix metalloprotease-2 (MMP-2) gelatinolytic activity, in fibroblast growth factor-2-stimulated endothelial cells. These unbalanced pathways modify in vitro angiogenic steps, inhibiting chemoinvasion and stimulating tubulogenic activity. Conclusions: Our results suggest that the proangiogenic effect of low concentrations of 3ABA alerts on the efficacy of PARP inhibitors to potentiate anticancer therapy. Moreover, they indicate that endothelial chemoinvasion and tubulogenesis depend on distinct proteolytic pathways

Immagini di Istopatologia : Atlante per le esercitazioni di Patologia Generale

This collection of images of Histopathology is the fruit of the authors\u27 thirty years\u27 experience in the performance of practical exercises in General Pathology. It is aimed at students attending lessons of General Pathology on the Degree Courses in Medical Surgery and Biological Sciences. It does not aspire either to be complete from the point of view of the various organic pathologies, or to replace direct and personal observation of the histological preparations through the microscope, but is rather intended as an aid to students preparing for the exam. It does not include the rudiments of cytology and microscopic anatomy, which it is assumed have already been mastered by those approaching General Histopathology, nor are histopathological phenomena systematically addressed, for which the reader is referred to textbooks on General Pathology. The 44 preparations presented here have been grouped in line with the main arguments of General Pathology: Cellular Degeneration, Inflammation, Neoplasia both benign and malign, and Vascular Pathology. They have been selected for their didactic significance and the simplicity and clarity of the lesions present, without taking into account the information to be derived from the clinical case history. The images of the preparations, in which the best possible quality of reproduction has been sought, are presented in progressive enlargements and are accompanied by brief descriptions comprising the explanations essential for identification of the characteristic aspects of the elementary lesion, as well as any eventual defects in the preparations themselves. Effectively, the objective of the work is to enable the student to exercise his understanding of the images. For this reason the casuistics included is as essential as possible, and the method of presentation utilised is designed to avoid mere visual memorisation, stimulating first analysis and then synthesis, and the development of individual logical skills so as to indicate whether aspects of cellular pathology, inflammation or neoplasia are present.Questa raccolta di immagini di Istopatologia \ue8 frutto dell\u27esperienza trentennale degli autori nello svolgimento delle esercitazioni pratiche di Patologia Generale. Essa \ue8 rivolta agli studenti che frequentano le lezioni di Patologia Generale dei Corsi di Laurea in Medicina e Chirurgia e di Scienze Biologiche. Non ha l\u27ambizione n\ue9 di essere completa da un punto di vista delle varie patologie d\u27organo, n\ue9 di sostituire l\u27osservazione diretta e personale al microscopio dei preparati istologici, ma vuole essere un aiuto per lo studente che si appresta a preparare l\u27esame. Non sono state riportate nozioni di citologia e anatomia microscopica che devono essere gi\ue0 possedute da chi si appresta allo studio della Istopatologia Generale, n\ue9 viene fornita alcuna trattazione sistematica dei fenomeni istopatologici, per i quali si rimanda a testi di Patologia Generale. I preparati presentati, in numero di 44, sono stati raggruppati secondo i principali argomenti della Patologia Generale: Degenerazioni Cellulari, Infiammazioni, Neoplasie sia benigne che maligne e Patologia Vascolare. Essi sono stati scelti per la loro valenza didattica e per la semplicit\ue0 e chiarezza delle lesioni presenti e prescindono da informazioni ricavabili dalla storia clinica del caso. Le immagini dei preparati, di cui si \ue8 cercata al massimo la bont\ue0 della riproduzione, sono presentate ad ingrandimenti crescenti e sono accompagnate da una breve descrizione che riporta le spiegazioni essenziali per poter individuare gli aspetti caratteristici della lesione elementare, nonch\ue9 eventuali difetti delle preparazioni. La finalit\ue0 dell\u27opera \ue8 infatti quella di permettere allo studente di esercitarsi alla comprensione delle immagini: abbiamo infatti riportato una casistica il pi\uf9 essenziale possibile ed \ue8 stato utilizzato un metodo di presentazione atto ad evitare la semplice memorizzazione visiva, stimolando ad un esercizio di analisi prima e sintesi poi, e per sviluppare le propri capacit\ue0 logiche onde evidenziare se siano presenti aspetti di patologia cellulare, o di infiammazione, o di neoplasia

Immagini di Istopatologia

This collection of images of Histopathology is the fruit of the authors' thirty years' experience in the performance of practical exercises in General Pathology. It is aimed at students attending lessons of General Pathology on the Degree Courses in Medical Surgery and Biological Sciences. It does not aspire either to be complete from the point of view of the various organic pathologies, or to replace direct and personal observation of the histological preparations through the microscope, but is rather intended as an aid to students preparing for the exam. It does not include the rudiments of cytology and microscopic anatomy, which it is assumed have already been mastered by those approaching General Histopathology, nor are histopathological phenomena systematically addressed, for which the reader is referred to textbooks on General Pathology. The 44 preparations presented here have been grouped in line with the main arguments of General Pathology: Cellular Degeneration, Inflammation, Neoplasia both benign and malign, and Vascular Pathology. They have been selected for their didactic significance and the simplicity and clarity of the lesions present, without taking into account the information to be derived from the clinical case history. The images of the preparations, in which the best possible quality of reproduction has been sought, are presented in progressive enlargements and are accompanied by brief descriptions comprising the explanations essential for identification of the characteristic aspects of the elementary lesion, as well as any eventual defects in the preparations themselves. Effectively, the objective of the work is to enable the student to exercise his understanding of the images. For this reason the casuistics included is as essential as possible, and the method of presentation utilised is designed to avoid mere visual memorisation, stimulating first analysis and then synthesis, and the development of individual logical skills so as to indicate whether aspects of cellular pathology, inflammation or neoplasia are present