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Protein interacting with carboxyl terminus 1 (PICT-1) is a nucleolar protein shown to act as a tumor suppressor that interacts with PTEN, or in a contrasting manner to facilitate the accessibility of p53 to ubiquitination and degradation, thus to function as an oncogene. The aim of the study was to examine the potential role of PICT-1 in neuroendocrine neoplasm (NEN) tumorigenesis and response to mTOR inhibitor treatment. PICT-1 was overexpressed in medullary thyroid (TT) and pancreatic (BON1) NEN cell lines using lentiviral vector. Whereas in BON1 cells PICT-1 overexpression exhibited no significant impact, in TT cells it induced the appearance of p53β lacking the C-terminus end. This was accompanied by a robust decrease in p21 expression and elevation of cell viability. Remarkably, PICT-1 overexpression completely reversed the reduction in cell viability of medullary thyroid neoplasm cells induced by everolimus, a therapeutic option for patients with progressive NENs. mTOR pathway investigations revealed that PICT-1 overexpression induced a reduction in PTEN expression and a robust increase in the expression level of phospho-Akt-Ser47 only partially inhibited by everolimus. These findings suggest a possible role of PICT-1 in the spliceosome machinery and provide functional involvement of PICT-1 in the complex network of mTOR.

The lactose breath test (LBT) is the standard technique for diagnosis of lactose malabsorption. However, it is time-consuming, strenuous for the patient and has been reported to have low sensitivity. The lactose intolerance quick test (LIQT) measures lactase activity in duodenal biopsies and may be performed as part of upper gastrointestinal endoscopy. The purpose of this study was to assess the role of the LBT and LIQT in the case management of suspected lactose malabsorption. The study group included 69 consecutive patients evaluated by the LBT followed by the LIQT. The test results were compared, and the sensitivity, specificity, and predictive values of the LBT were calculated. Mean age of the patients was 54.4 years, male/female ratio was 1:3, and mean body mass index was 25.2. None had celiac disease on duodenal biopsy. The LIQT was positive for hypolactasia in 55 patients (80 %): mild in 14 (25 %) and severe in 41 (75 %); 10 (18 %) were symptomatic during the LBT. The LBT was positive for lactose malabsorption in 32 patients (46 %). Of the 37 patients with normal findings on the LBT, 24 (65 %) had positive findings on the LIQT: 11 (30 %) mild hypolactasia, 13 (35 %) severe hypolactasia. In one case, the LBT was positive and the LIQT was negative. The LBT had a sensitivity of 56 %, specificity 93 %, positive predictive value 97 %, and negative predictive value 35 %. The LBT may serve as a diagnostic screening tool for lactose malabsorption. Symptomatic patients with negative LBT results should be referred for second-line testing with the LIQT.