The TRIM proteins in cancer: from expression to emerging regulatory mechanisms.

New clinical evidence suggests that dysregulation of the ubiquitin-mediated destruction of tumor suppressors or oncogene products is probably engaged in the etiology of leukemia and carcinoma. The superfamily of tripartite motif (TRIM)-containing protein family is among the biggest recognized single protein RING finger E3 ubiquitin ligases that are considered vital carcinogenesis regulators, which is not shocking since TRIM proteins are engaged in various biological processes, including cell growth, development, and differentiation; hence, TRIM proteins' alterations may influence apoptosis, cell proliferation, and transcriptional regulation. In this review article, the various mechanisms through which TRIM proteins exert their role in the most prevalent malignancies including lung, prostate, colorectal, liver, breast, brain cancer, and leukemia are summarized.

Psychological impact of multigene cancer panel testing in patients with a clinical suspicion of hereditary cancer across Spain.

OBJECTIVE: Patients' psychological reactions to multigene cancer panel testing might differ compared with the single-gene testing reactions because of the complexity and uncertainty associated with the different possible results. Understanding patients' preferences and psychological impact of multigene panel testing is important to adapt the genetic counselling model. METHODS: One hundred eighty-seven unrelated patients with clinical suspicion of hereditary cancer undergoing a 25-gene panel test completed questionnaires after pretest genetic counselling and at 1 week, 3 months, and 12 months after results to elicit their preferences regarding results disclosure and to measure their cancer worry and testing-specific distress and uncertainty. RESULTS: A pathogenic variant was identified in 38 patients (34 high penetrance and 4 moderate penetrance variants), and 54 patients had at least one variant of uncertain significance. Overall, cancer panel testing was not associated with an increase in cancer worry after results disclosure (P value = .87). Twelve months after results, carriers of a moderate penetrance variant had higher distress and uncertainty scores compared with carriers of high penetrance variants. Cancer worry prior to genetic testing predicted genetic testing specific distress after results, especially at long term (P value <.001). Most of the patients reported the wish to know all genetic results. CONCLUSIONS: Our results suggest that patients can psychologically cope with cancer panel testing, but distress and uncertainty observed in carriers of moderate penetrance cancer variants in this cohort warrant further research.

Helicobacter pylori and bleeding duodenal ulcer: prevalence of the infection and role of non-steroidal anti-inflammatory drugs.

BACKGROUND: Several authors have reported low prevalence of Helicobacter pylori infection in patients with upper gastrointestinal bleeding (UGIB). Our aim was to study the prevalence of H. pylori in bleeding duodenal ulcer (DU), with both invasive and non-invasive methods, and to assess the role of non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: Ninety-two patients with bleeding DU were prospectively studied. The use of NSAIDs was evaluated by specific questionnaire. As a control group, 428 patients undergoing outpatient evaluation for the investigation of dyspepsia and found to have a DU at endoscopy were included. At endoscopy, two antral biopsies were obtained (H&E stain). A 13C-urea breath test was carried out in all patients. Breath test was repeated in patients treated with omeprazole during the hospitalization if H. pylori was not detected with the first test. RESULTS: Gastric biopsies could be obtained in 39 patients with UGIB. Three patients with UGIB treated with omeprazole and being H. pylori-negative with the first breath test were finally considered infected with the second test. Overall, 92.4% (95% CI, 85%-96%) of the patients with UGIB were infected (89.7% with histology and 92.4% with breath test (P = 0.15)). Concordance kappa value for both diagnostic tests was 0.64. NSAID intake was more frequent in patients with UGIB (34%) than in those without UGIB (5.6%) (P < 0.001), while H. pylori infection was less frequent in patients with UGIB (92.4% (85%-96%)) than in those without UGIB (99.1% (98%-100%); P < 0.001). Even in patients with UGIB, NSAID intake was the only risk factor in 5% of cases. The proportion of cases without H. pylori infection and without NSAID intake was very low in both bleeding and non-bleeding ulcers (2% and 0.5%, respectively; P = 0.146). H. pylori prevalence in bleeding ulcers was of 84% (67%-93%) in patients with NSAID intake, and 96.7% (89%-99%) when patients taking NSAIDs were excluded. In the multivariate analysis, NSAID intake (odds ratio, 9.8 (5.2-18.4)) correlated with UGIB; however, neither H. pylori status nor the interaction between H. pylori infection and NSAID intake correlated with UGIB. In the multivariate analysis in the subgroup of patients with UGIB, NSAID use was the only variable which correlated with H. pylori prevalence (odds ratio, 0.18 (0.03-0.97)). CONCLUSIONS: The most important factor associated with H. pylori-negative bleeding DU is NSAID use, and if this factor is excluded prevalence of infection is almost 100% (97%), similar to that found in patients with non-bleeding DU (and without NSAID intake). Bleeding DU patients with neither H. pylori infection nor NSAID use are extremely rare (only 2%), which suggests that the pathogenesis of bleeding DU is similar to that of non-complicated DU disease.