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A pre-existing population of ZEB2+ quiescent cells with stemness and mesenchymal features dictate chemoresistance in colorectal cancer

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.

Tumori colorettali: alcuni pazienti a rischio con overdrive immune

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; Surgical Treatment of a Disabling Deformity

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.

Appendiceal abscess in a giant left‑sided inguinoscrotal hernia: a rare case of Amyand hernia

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

SpringerPlus.2015, 4:378

DOI: 10.1186/s40064-015-1162-9

URL: http://www.springerplus.com/content/4/1/378

Rai3 - Elisir: Emorroidi, sintomi principali e terapie

Rai3 Elisir

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.