OCT4 controls mitotic stability and inactivates the RB tumor suppressor pathway to enhance ovarian cancer aggressiveness.

OCT4 (Octamer-binding transcription factor 4) is essential for embryonic stem cell self-renewal. Here we show that OCT4 increases the aggressiveness of high-grade serous ovarian cancer (HG-SOC) by inactivating the Retinoblastoma tumor suppressor pathway and enhancing mitotic stability in cancer cells. OCT4 drives the expression of Nuclear Inhibitor of Protein Phosphatase type 1 (NIPP1) and Cyclin F (CCNF) that together inhibit Protein Phosphatase 1 (PP1). This results in pRB hyper-phosphorylation, accelerated cell proliferation and increased in vitro tumorigenicity of ovarian cancer cells. In parallel, OCT4 and NIPP1/CCNF drive the expression of the central Chromosomal Passenger Complex (CPC) components, Borealin, Survivin and the mitotic kinase Aurora B, promoting the clustering of supernumerary centrosomes to increase mitotic stability. Loss of OCT4 or NIPP1/CCNF results in severe mitotic defects, multipolar spindles and supernumerary centrosomes, finally leading to the induction of apoptosis. These phenotypes were recapitulated in different cancer models indicating general relevance for human cancer. Importantly, activation of these parallel pathways leads to dramatically reduced overall survival of HG-SOC patients. Altogether, our data highlights an unprecedented role for OCT4 as central regulator of mitotic fidelity and RB tumor suppressor pathway activity. Disrupting this pathway represents a promising strategy to target an aggressive subpopulation of HG-SOC cells.

[The prevalence of agenesis in a sample of 2954 school-age subjects in Trieste Province]. / Prevalenza delle agenesie in un campione di 2954 soggetti in età scolare nella provincia di Trieste.

The paper reports the results of an epidemiological study on the prevalence of agenesis in school-aged population of the province of Trieste carried out in a sample group of 2954 6-, 10- and 12-year-old subjects. Fifty-one subjects appeared to the affected by single or multiple dental agenesis. The distribution of agenesis is illustrated in the tables and figures. Results are compared with other previously published compared reports.

[Hypertrophy of the concha of the auricle. Details of the technic]. / Ipertrofia della conca del padiglione auricolare. Un dettaglio di tecnica.

Ear concha hypertrophy corrected by elliptical conchal excision often resulted in deformity due to lateral deviation of the anterior part of the concha. A modification of the method allows to avoid that deviation: the conchal ellipse is left connected to the conchal floor, is weakened by half thickness incisions parallel to the edge; the conchal floor thus flattened is sutured to the lateral side of the head by non absorbable suture.

[Clinico-statistical considerations on a sample of school-age population in the Province of Trieste. I. Period of eruption of the lst molars and change in permanent incisors]. / Considerazioni clinico-statistiche su di un campione di popolazione in età scolare nella Provincia di Trieste. Nota I. Epoca di eruzione dei primi molari e permuta degli incisivi permanenti.

The phenomenon relating to the period of change of the incisors and eruption of the first permanent molar were studied in a group of 343 Trieste school children. Both deciduous and permanent teeth were examined. The results were processed on a computer and are presented in graph form.

[Clinico-statistical considerations on a sample of school-age population in the Province of Trieste. II. Period of eruption of the second molars and change of the canines and 1st and 2d permanent premolars]. / Considerazioni clinico-statistiche su di un campione di popolazione in età scolare nella Provincia di Trieste. Nota II. Epoca di eruzione dei secondi molari e permuta dei canini, primi e secondi premolari permanenti.

The phenomena relating to the period of change of the canines and the first and second permanent premolars and of the eruption of the second permanent molar were studied in a group of 343 Trieste school children. Both deciduous and permanent teeth were examined. The results were processed on a computer, and are presented in graph form.

[Clinico-statistical considerations on a sample of school-age population in the Province of Trieste. 3. Incidence of dental and orthognatodontic pathology]. / Considerazioni clinico-statistiche su di un campione di popolazione in età scolare nella Provincia di Trieste. Nota III. Incidenza della patologia dentaria ed ortognatodontica.

Dental and orthognathodontic pathology and its conservative treatment were investigated in a sample of 343 Trieste school children. The results were processed on a computer and are presented in graph form. The epidemiological indices suggested by the WHO were also calculated.