Intervista al Prof. Gianfranco Gualdi, Responsabile Radiologia d’Urgenza Azienda Policlinico Umberto I Università “La Sapienza” di Roma
Nella prevenzione dei tumori e in particolare del tumore all'intestino; evoluzione della radiologia: colonscopia virtuale vs tradizionale, prescrizione PET (Positron Emission Tomography), TAC con PET, rischi della TAC, rischi connessi ai campi magnetici.
Background: Quiescent/slow cycling cells have been identified in several tumors and correlated with therapy resistance. However, the features of chemoresistant populations and the molecular factors linking quiescence to chemoresistance are largely unknown.
Methods: A population of chemoresistant quiescent/slow cycling cells was isolated through PKH26 staining (which allows to separate cells on the basis of their proliferation rate) from colorectal cancer (CRC) xenografts and subjected to global gene expression and pathway activation analyses. Factors expressed by the quiescent/slow
cycling population were analyzed through lentiviral overexpression approaches for their ability to induce a dormant chemoresistant state both in vitro and in mouse xenografts. The correlation between quiescence-associated factors, CRC consensus molecular subtype and cancer prognosis was analyzed in large patient datasets.
Results: Untreated colorectal tumors contain a population of quiescent/slow cycling cells with stem cell features (quiescent cancer stem cells, QCSCs) characterized by a predetermined mesenchymal-like chemoresistant phenotype. QCSCs expressed increased levels of ZEB2, a transcription factor involved in stem cell plasticity and epithelial-mesenchymal transition (EMT), and of antiapototic factors pCRAF and pASK1. ZEB2 overexpression upregulated pCRAF/pASK1 levels resulting in increased chemoresistance, enrichment of cells with stemness/EMT traits and proliferative slowdown of tumor xenografts. In parallel, chemotherapy treatment of tumor xenografts induced the prevalence of QCSCs with a stemness/EMT phenotype and activation of the ZEB2/pCRAF/pASK1 axis, resulting in a chemotherapy-unresponsive state. In CRC patients, increased ZEB2 levels correlated with worse relapse-free survival and were strongly associated to the consensus molecular subtype 4 (CMS4) characterized by dismal prognosis, decreased proliferative rates and upregulation of EMT genes.
Conclusions: These results show that chemotherapy-naive tumors contain a cell population characterized by a coordinated program of chemoresistance, quiescence, stemness and EMT. Such population becomes prevalent upon drug treatment and is responsible for chemotherapy resistance, thus representing a key target for more effective therapeutic approaches.
L’infiltrazione di cellule immunitarie nei tumori è di solito associata ad esiti favorevoli, ma talvolta nei tumori colorettali accade l’opposto. Uno strumento chiamato immunoscore, creato per prevedere le recidive di questi tumori, potrebbe riclassificare correttamente i pazienti ad alto rischio come a basso rischio.
Traumatic cloaca is a disabling deformity of the anus and vagina caused by the severe damage of the sphincter apparatus and of the perineal body, resulting in a common aperture for the rectum and vagina, as in congenital cloaca [2-4,9].
The most common cause is major obstetric injury occurred by median episiotomies that lead to third and fourth degree perineal lacerations, unrecognized or not repaired properly. The incidence is approximately 0.3% of all complicated vaginal deliveries. The resulting deformity is characterized by three-dimensional destruction of the perineal body, anterior disruption of the sphincter complex and loss of the distal rectovaginal septum of varying length. [1-4,7, 9] Other rare causes of traumatic cloaca may be severe injuries in women victims of sexual violence or by grave accidents in sports like cycling.
Pubblicazione sulla prestigiosa rivista "Springer Plus" del Case Study
Autori: Massimo Mongardini, Alessandro Maturo, Livia De Anna, Giada Livadoti, Valerio D’Orazi, Paolo Urciuoli
and Filippo Custureri
Elisir, in onda martedì 21 aprile 2015 su Rai3. Si parla delle emorroidi e di quali sono i sintomi principali: prurito o bruciore e sanguinamento lieve. Possono scomparire? Ci potranno essere delle recidive? Le terapie? Se ne parla con il professor Massimo Mongardini, chirurgo all'Università La Sapienza di Roma Policlinico Umberto I, intervistato da Michele Mirabella.