Correction to: NFATc2 is an intrinsic regulator of melanoma dedifferentiation.

In Fig. 6e, the authors noticed that wrong blots for MITF, MART-1 expression/modulation, and for ß-actin were presented, due to the similarity with experiments shown in Figure 5c. Correct MITF, MART-1, and ß-actin blots were added to the revised Fig. 6 shown in the associated Correction. The meaning of the results shown in Fig.6e, as well as the conclusions of this paper were not affected, and the authors regret for this error. These errors have not been fixed in the original Article.

NFATc2 is an intrinsic regulator of melanoma dedifferentiation.

Melanoma dedifferentiation, characterized by the loss of MITF and MITF regulated genes and by upregulation of stemness markers as CD271, is implicated in resistance to chemotherapy, target therapy and immunotherapy. The identification of intrinsic mechanisms fostering melanoma dedifferentiation may provide actionable therapeutic targets to improve current treatments. Here, we identify NFATc2 transcription factor as an intrinsic regulator of human melanoma dedifferentiation. In panels of melanoma cell lines, NFATc2 expression correlated inversely with MITF at both mRNA and protein levels. NFATc2(+/Hi) melanoma cell lines were CD271(+) and deficient for expression of melanocyte differentiation antigens (MDAs) MART-1, gp100, tyrosinase and of GPNMB, PGC1-α and Rab27a, all regulated by MITF. Targeting of NFATc2 by small interfering RNA, short hairpin RNA and by an NFATc2 inhibitor upregulated MITF, MDAs, GPNMB, PGC-1α, tyrosinase activity and pigmentation and suppressed CD271. Mechanistically, we found that NFATc2 controls melanoma dedifferentiation by inducing expression in neoplastic cells of membrane-bound tumor necrosis factor-α (mTNF-α) and that melanoma-expressed TNF-α regulates a c-myc-Brn2 axis. Specifically, NFATc2, mTNF-α and expression of TNF receptors were significantly correlated in panels of cell lines. NFATc2 silencing suppressed TNF-α expression, and neutralization of melanoma-expressed TNF-α promoted melanoma differentiation. Moreover, silencing of NFATc2 and TNF-α neutralization downmodulated c-myc and POU3F2/Brn2. Brn2 was strongly expressed in NFATc2(+/Hi) MITF(Lo) cell lines and its silencing upregulated MITF. Targeting of c-myc, by silencing or by a c-myc inhibitor, suppressed Brn2 and upregulated MITF and MART-1 in melanoma cells. The relevance of NFATc2-dependent melanoma dedifferentiation for immune escape was shown by cytolytic T-cell assays. NFATc2(Hi) MITF(Lo) MDA(Lo) HLA-A2.1(+) melanoma cells were poorly recognized by MDA-specific and HLA-A2-restricted CTL lines, but NFATc2 targeting significantly increased CTL-mediated tumor recognition. Taken together, these results suggest that the expression of NFATc2 promotes melanoma dedifferentiation and immune escape.

Bowel cleansing before CT colonography: comparison between two minimal-preparation regimens.

AIM: To compare two regimens of reduced bowel preparation and faecal tagging for CT colonography. MATERIALS AND METHODS: Single centre, prospective, randomized, noninferiority study, in which 52 consecutive adults underwent routine CT colonography. Patients, following a three-day low-fibre diet, received one of the two reduced preparations: 1-L polyethylene glycol and four tablets of bisacodyl in association with 90 mL of Iopamidol for faecal tagging administered on the same day as CTC examination (group 1); or a standard "iodine-only" preparation, consisting in 180 ml of Iopamidol the day before the examination (group 2). Primary outcome was the overall quality of bowel preparation. RESULTS: Twenty-six patients per group were included. Per segment analysis showed preparation of diagnostic quality in 97.4% of segments in group 1 and in 95.5% in group 2 (p = ns). Per-patient analysis showed optimal quality of preparation in 76.9% of patients in group 1 and in 84.6% in group 2 (p = ns). Patient tolerability to both preparations was not different. CONCLUSION: A limited bowel preparation consisting of 1-L PEG and four tablets of bisacodyl in association with 90 mL of Iodine for faecal tagging administered on the same day as CTC examination is feasible and offers bowel cleansing comparable to "iodine-only" preparation. KEY POINTS: • Low-dose PEG bisacodyl and Iopamidol preparation is feasible, providing adequate bowel cleansing. • Faecal tagging is not different from the two limited preparations. • Patient tolerability to the two colon cleansing regimens is similar.

Gallbladder and muscular endometriosis: a case report.

A 55-year-old woman referred to Radiology Department, with abdominal mass and chronic indefinite and vague abdominal pain, most severe in right hypochondrium and accentuated during menstruation. A history of two cesarean sections was revealed. The patient underwent an ultrasound and Computed Tomography with intravenous contrast media revealing the presence of gallbladder and abdominal wall hyperenhancing masses. Finally, Magnetic Resonance study with intravenous administration of paramagnetic contrast media confirmed the involvement of gallbladder by a solid tissue and the presence of a solid nodule on the abdominal wall. Considering imaging features and the contrast enhancement of the nodules, the patient was sent to surgery. Surgical removal of both gallbladder and abdominal solid implant was performed and histology confirmed the diagnosis of gallbladder and abdominal wall endometriosis.

Peritoneal carcinomatosis: imaging with 64-MDCT and 3T MRI with diffusion-weighted imaging.

Peritoneal carcinomatosis is usually associated with a poor overall survival rate. Recently, introduction of more aggressive surgical treatment and intraperitoneal chemotherapy appears to significantly increase the overall survival rate for these patients. A detailed preoperative assessment of peritoneal carcinomatosis could be very challenging in the field of imaging, but a new aggressive surgical approach requires an accurate preoperative assessment of the disease. Cross-sectional imaging using CT and MRI with diffusion-weighted imaging (DWI) sequences is important for appropriate management of patients with peritoneal carcinomatosis. Appreciation of the spectrum of diagnostic patterns and pitfalls as well as different sites of involvement of peritoneal carcinomatosis using CT and DWI is crucial for appropriate surgical treatment.

High positive predictive value of CT colonography in a referral centre.

AIM: To assess the positive predictive value (PPV) of CTC in the clinical routine of a dedicated referral centre. MATERIAL AND METHODS: All consecutive patients referred for CTC between May 2009 and May 2010 were considered for inclusion in this study. All the patients who, following the diagnosis of a>6 mm polyp or mass at CTC, underwent a post-CTC colonoscopy within eight weeks from diagnosis were included. Per patient PPV for lesions, adenomas and advanced neoplasia was calculated. Chi-square test was used for statistical comparison, and a p value<0.05 was considered to be statistically significant. RESULTS: 516 patients were included in the study. Of them, 76 (14%) patients had at least one lesion≥6 mm on CTC. Overall, 59 (11%) patients were diagnosed at CTC with at least one polyp, 12 (2%) with a flat lesions, and 5 (1%) with a mass. Per-patient PPVs for any lesion>6 mm, neoplasia, and advanced neoplasia were 96% (95% CI: 92-100%), 68.4% (95% CI: 58-79%), and 30% (95% CI: 20-41%), respectively. PPV for neoplasia and advanced neoplasia was substantially higher for >10 mm lesions. CONCLUSION: In dedicated centers, CTC appears to be a highly specific procedure, characterized by a very low rate of false-positive results for >6 mm lesions.