The development and progression of colorectal cancer (CRC), a major cause of cancer-related death in the western world, is accompanied with alterations of sphingolipid (SL) composition in colon tumors. A number of enzymes involved in the SL metabolism have been found to be deregulated in human colon tumors, in experimental rodent studies, and in human colon cancer cells in vitro. Therefore, the enzymatic pathways that modulate SL levels have received a significant attention, due to their possible contribution to CRC development, or as potential therapeutic targets. Many of these enzymes are associated with an increased sphingosine-1-phosphate/ceramide ratio, which is in turn linked with increased colon cancer cell survival, proliferation and cancer progression. Nevertheless, more attention should also be paid to the more complex SLs, including specific glycosphingolipids, such as lactosylceramides, which can be also deregulated during CRC development. In this review, we focus on the potential roles of individual SLs/SL metabolism enzymes in colon cancer, as well as on the pros and cons of employing the current in vitro models of colon cancer cells for lipidomic studies investigating the SL metabolism in CRC.

Background: Dishevelled (DVL) is an essential component of the Wnt signaling cascades. Function of DVL is controlled by phosphorylation but the molecular details are missing. DVL3 contains 131 serines and threonines whose phosphorylation generates complex barcodes underlying diverse DVL3 functions. In order to dissect the role of DVL phosphorylation we analyzed the phosphorylation of human DVL3 induced by previously reported (CK1ε, NEK2, PLK1, CK2α, RIPK4, PKCδ) and newly identified (TTBK2, Aurora A) DVL kinases.Methods: Shotgun proteomics including TiO₂enrichment of phosphorylated peptides followed by liquid chromatography tandem mass spectrometry on immunoprecipitates from HEK293T cells was used to identify and quantify phosphorylation of DVL3 protein induced by 8 kinases. Functional characterization was performed by in-cell analysis of phospho-mimicking/non-phosphorylatable DVL3 mutants and supported by FRET assays and NMR spectroscopy.Results: We used quantitative mass spectrometry and calculated site occupancies and quantified phosphorylation of > 80 residues. Functional validation demonstrated the importance of CK1ε-induced phosphorylation of S268 and S311 for Wnt-3a-induced β-catenin activation. S630–643 cluster phosphorylation by CK1, NEK2 or TTBK2 is essential for even subcellular distribution of DVL3 when induced by CK1 and TTBK2 but not by NEK2. Further investigation showed that NEK2 utilizes a different mechanism to promote even localization of DVL3. NEK2 triggered phosphorylation of PDZ domain at S263 and S280 prevents binding of DVL C-terminus to PDZ and promotes an open conformation of DVL3 that is more prone to even subcellular localization.Conclusions: We identify unique phosphorylation barcodes associated with DVL function. Our data provide an example of functional synergy between phosphorylation in structured domains and unstructured IDRs that together dictate the biological outcome.Graphical

The development of colon cancer, one of the most common malignancies, is accompanied with numerous lipid alterations. However, analyses of whole tumor samples may not always provide an accurate description of specific changes occurring directly in tumor epithelial cells. Here, we analyzed in detail the phospholipid (PL), lysophospholipid (lysoPL), and fatty acid (FA) profiles of purified EpCAM⁺ cells, isolated from tumor and adjacent non-tumor tissues of colon cancer patients. We found that a number of FAs increased significantly in isolated tumor cells, which also included a number of long polyunsaturated FAs. Higher levels of FAs were associated with increased expression of FA synthesis genes, as well as with altered expression of enzymes involved in FA elongation and desaturation, including particularly fatty acid synthase, stearoyl-CoA desaturase, fatty acid desaturase 2 and ELOVL5 fatty acid elongase 5 We identified significant changes in ratios of specific lysoPLs and corresponding PLs. A number of lysophosphatidylcholine and lysophosphatidylethanolamine species, containing long-chain and very-long chain FAs, often with high numbers of double bonds, were significantly upregulated in tumor cells. Increased de novo synthesis of very long-chain FAs, or, altered uptake or incorporation of these FAs into specific lysoPLs in tumor cells, may thus contribute to reprogramming of cellular phospholipidome and membrane alterations observed in colon cancer.

Chest X-ray (CXR) is one of the most common radiological examinations for both nonemergent and emergent clinical indications, but human error or lack of prioritization of patients can hinder timely interpretation. Deep learning (DL) algorithms have proven to be useful in the assessment of various abnormalities including tuberculosis, lung parenchymal lesions, or pneumothorax. The deep learning–based automatic detection algorithm (DLAD) was developed to detect visual patterns on CXR for 12 preselected findings. To evaluate the proposed system, we designed a single-site retrospective study comparing the DL algorithm with the performance of five differently experienced radiologists. On the assessed dataset (n = 127) collected from the municipal hospital in the Czech Republic, DLAD achieved a sensitivity (Se) of 0.925 and specificity (Sp) of 0.644, compared to bootstrapped radiologists’ Se of 0.661 and Sp of 0.803, respectively, with statistically significant difference. The negative likelihood ratio (NLR) of the proposed software (0.12 (0.04–0.32)) was significantly lower than radiologists’ assessment (0.42 (0.4–0.43), p < 0.0001). No critical findings were missed by the software.

Background: Microparticles (MPs) are small (0.1–1 μm) cell-derived vesicles released during activation or apoptosis, with a surface-exposed phosphatidylserine along with antigens indicating the cellular origin. The level of MPs is known to be elevated in thromboembolic diseases and malignancies; it is believed that MPs are not only amplifying but can also initiate the thrombogenesis...

Aims: To describe the ultrasound features of benign struma ovarii that often mimic ovarian cancer in the background of complex clinical and histopathological pictures. Material and methods: We retrospectively identified patients with histologically confirmed benign struma ovarii, treated in our institution between 2003–2016 with complete imaging, clinical, nd histopathological data available. Ultrasound findings were drawn from images, and reports using terms and definitions of the International Ovarian Tumor Analysis group and pattern recognition description was applied. Results: In all, 19 patients were identified; 10 with pure and 9 with impure struma. Median age was 47 (range 24–69); 10 (53%) were premenopausal. Only four (21%) patients presented with pain, others were asymptomatic. Using pattern recognition, 74% strumas (14/19) were uni-/multilocular solid or solid tumors. The solid components were roundish with smooth contours. Six struma pearls were detected. The subjective color score was moderate or abundant in the majority of solid components. Only 5 (26%) tumors were purely cystic. Conclusions: The ultrasound characteristics differ widely from typical mature ovarian teratoma. Features such as, solid roundish components with smooth contours, struma pearls, acoustic shadowing and occasionally signs of dermoid are clues and may help preoperatively to differentiate benign struma from malignant adnexal lesions.