S100A4 interacts with p53 in the nucleus and promotes p53 degradation.

S100A4 is a small calcium-binding protein that is commonly overexpressed in a range of different tumor types, and it is widely accepted that S100A4 has an important role in the process of cancer metastasis. In vitro binding assays has shown that S100A4 interacts with the tumor suppressor protein p53, indicating that S100A4 may have additional roles in tumor development. In the present study, we show that endogenous S100A4 and p53 interact in complex samples, and that the interaction increases after inhibition of MDM2-dependent p53 degradation using Nutlin-3A. Further, using proximity ligation assay, we show that the interaction takes place in the cell nucleus. S100A4 knockdown experiments in two p53 wild-type cell lines, A549 and HeLa, resulted in stabilization of p53 protein, indicating that S100A4 is promoting p53 degradation. Finally, we demonstrate that S100A4 knockdown leads to p53-dependent cell cycle arrest and increased cisplatin-induced apoptosis. Thus, our data add a new layer to the oncogenic properties of S100A4 through its inhibition of p53-dependent processes.

The EGFR family members sustain the neoplastic phenotype of ALK+ lung adenocarcinoma via EGR1.

In non-small cell lung cancer (NSCLC), receptor tyrosine kinases (RTKs) stand out among causal dominant oncogenes, and the ablation of RTK signaling has emerged as a novel tailored therapeutic strategy. Nonetheless, long-term RTK inhibition leads invariably to acquired resistance, tumor recurrence and metastatic dissemination. In ALK+ cell lines, inhibition of ALK signaling was associated with coactivation of several RTKs, whose pharmacological suppression reverted the partial resistance to ALK blockade. Remarkably, ERBB2 signaling synergized with ALK and contributed to the neoplastic phenotype. Moreover, the engagement of wild-type epidermal growth factor receptor or MET receptors could sustain cell viability through early growth response 1 (EGR1) and/or Erk1/2; Akt activation and EGR1 overexpression prevented cell death induced by combined ALK/RTK inhibition. Membrane expression of ERBB2 in a subset of primary naive ALK+ NSCLC could be relevant in the clinical arena. Our data demonstrate that the neoplastic phenotype of ALK-driven NSCLC relays 'ab initio' on the concomitant activation of multiple RTK signals via autocrine/paracrine regulatory loops. These findings suggest that molecular and functional signatures are required in de novo lung cancer patients for the design of efficacious and multi-targeted 'patient-specific' therapies.

[Retropubic adenectomy (Millin's technique). Our experience]. / Adenomectomia retropubica secondo Millin. Nostra esperienza.

From January 1983 to December 1993, on 1917 ptz who underwent to operations for BPH, 1532 pts (80%) had transurethral adenomectomy, and 385 pts (20%) had retropubic adenomectomy. The prostatic weight, obtained by ultrasound, is the factor which determines the kind of operations: transurethral adenomectomy if the prostate weight is lower than 50 gr, open surgery if it is more than 50 gr. In our experience about retropubic adenomectomy (Millin) we never had patient's death during operation or in the immediate post-operatively period. The early complications were 13.7%, and the late complications were 3.8%. The retropubic adenomectomy, when performed with right indications, is still valid.

Ciclopiroxolamine: clinical and microbiological considerations. Preliminary data.

Ciclopiroxolamine's action has been evaluated in 20 cases of dermatophytosis. The minimum inhibitory concentrations (MIC) for the strains was determined in vitro before treatment (To), after the 4th day (T4), and after the 7th day (T7) of treatment, in relation with the drug's fungicide effect. No significant variation was observed among the MIC values. By comparing the MIC of T4 versus the MIC of To a 0.93 coefficient of linear correlation was obtained while in comparing T7 versus T4 the coefficient was equivalent to 1.0. After 7 days of treatment 5 patients clinically recovered, 11 improved and 4 showed no improvement. Drug tolerance was excellent except for one case.