Radiomics-based prediction of microsatellite instability in colorectal cancer at initial computed tomography evaluation

Purpose

To predict microsatellite instability (MSI) status of colon cancer on preoperative CT imaging using radiomic analysis.

Methods

This retrospective study involved radiomic analysis of preoperative CT imaging of patients who underwent resection of stage II–III colon cancer from 2004 to 2012. A radiologist blinded to MSI status manually segmented the tumor region on CT images. 254 Intensity-based radiomic features were extracted from the tumor region. Three prediction models were developed with (1) only clinical features, (2) only radiomic features, and (3) “combined” clinical and radiomic features. Patients were randomly separated into training (n = 139) and test (n = 59) sets. The model was constructed from training data only; the test set was reserved for validation only. Model performance was evaluated using AUC, sensitivity, specificity, PPV, and NPV.

Results

Of the total 198 patients, 134 (68%) patients had microsatellite stable tumors and 64 (32%) patients had MSI tumors. The combined model performed slightly better than the other models, predicting MSI with an AUC of 0.80 for the training set and 0.79 for the test set (specificity = 96.8% and 92.5%, respectively), whereas the model with only clinical features achieved an AUC of 0.74 and the model with only radiomic features achieved an AUC of 0.76. The model with clinical features alone had the lowest specificity (70%) compared with the model with radiomic features alone (95%) and the combined model (92.5%).

Conclusions

Preoperative prediction of MSI status via radiomic analysis of preoperative CT adds specificity to clinical assessment and could contribute to personalized treatment selection.

     

Antiinflammatory Properties of Extracts and Compounds Isolated from Verbascum xanthophoeniceum Griseb

Verbascum xanthophoeniceum Griseb. is an endemic plant of the Balkan region, a representative of the genus Verbascum used in traditional medicine for respiratory and inflammatory disorders. The objective of this study was to evaluate in vivo and in vitro the antiinflammatory action of crude extract, different fractions and pure compounds obtained from V. xanthophoeniceum Griseb. Bioactive metabolites were isolated by the use of low‐pressure chromatographic separation. Crude methanol extract (CME) was applied in a model of paw oedema and different fractions and substances were tested in vitro for their effect on NO and cytokine production by peritoneal macrophages, and on the COX‐1 and COX‐2 expression. The CME exerted inhibition on cobra venom factor (CVF)‐induced oedema in mice, in correlation with reduced alternative pathway (AP) complement activity. A highly suppressive effect was expressed by nigroside VI on IL‐6 and NO production and by forsythoside B on TNF‐α production. Leucosceptoside B lowered NO release and COX‐1 expression in macrophages. Verbascum xanthophoeniceum could serve as a promising source of active compounds with antiinflammatory action, particularly in complement‐mediated disorders. Copyright © 2012 John Wiley & Sons, Ltd.     

Surveilling Russell body Helicobacter pylori-negative gastritis: A case report and review of literature

BACKGROUND Russell body gastritis(RBG) is very rare type of chronic inflammation of gastric mucosa. The pathologic hallmark of the disease is Russell bodies(RB) which represent accumulation of eosinophilic cytoplasmic inclusions in endoplasmic reticulum of mature plasma cells(Mott cells). Most published cases are associated with Helicobacter pylori(H. pylori) infection because of correlation between plasma cell activation and antigenic stimulation. There are insufficient data about H. pylori-negative RBG and very little is known about the natural course of the disease.CASE SUMMARY A 51-year-old male patient underwent endoscopic screening for mild iron deficiency anemia. Gastroscopy revealed diffuse hyperemia, edema and nodularity of the fundic and corpus mucosa. Due to non-specific endoscopic findings and iron-deficiency anemia our preliminary diagnosis was diffuse type of gastric carcinoma or gastric lymphoma. Biopsy specimens of gastric mucosa showed inflammatory infiltrate rich in Mott cells, consisting entirely of cytoplasmic RB. Absence of nuclear atypia and mitosis of the plasma cells, polyclonal pattern of the Mott cells and negative staining for cytokeratins favored diagnosis of RBG. The patient was treated with proton-pump inhibitor for 8 wk. Long-term clinical and endoscopic surveillance was scheduled. Albeit, there was no improvement in endoscopic features of the gastric mucosa in three consecutive gastroscopies, histopathological findings demonstrated that the chronic inflammatory infiltrate in the fundic mucosa is less pronounced, rich in plasma cells, with almost absent RB and Mott cells.CONCLUSION The prognosis of this entity is uncertain, that is why these patients are subjects of continuous follow up.     

Dynamic Ca(2+) signal modalities in the vascular endothelium

The endothelium is vital to normal vasoregulation. Although acute vasodilation associated with broad endothelial Ca(2+) elevation is well known, the control and targeting of Ca(2+) -dependent signals in the endothelium are poorly understood. Recent studies have revealed localized IP(3) -motivated Ca(2+) events occurring basally along the intima that may provide the fundamental basis for various endothelial influences. Here, we provide an overview of dynamic endothelial Ca(2+) signals and discuss the potential role of these signals in constant endothelial control of arterial tone and the titration of functional responses in vivo. In particular, we focus on the functional architecture contributing to the properties and ultimate impact of these signals, and explore new avenues in evaluating their prevalence and specific modalities in intact tissue. Finally, we discuss spatial and temporal effector recruitment through modification of these inherent signals. It is suggested that endothelial Ca(2+) signaling is a continuum in which the specific framework of store-release components and cellular targets along the endothelium allows for differential modes of Ca(2+) signal expansion and distinctive profiles of effector recruitment. The precise composition and distribution of these inherent components may underlie dynamic endothelial control and specialized functions of different vascular beds.     

The Effect of Surface Processing on the Shear Strength of Cobalt-Chromium Dental Alloy and Ceramics

Porcelain fused to metal is widespread dental prosthetic restoration. The survival rate of metal-ceramic restorations depends not only on the qualifications of dentists, dental technicians but also on the adhesive strength of ceramics to a metal frame. The goal of the research is to determine the optimal parameters of the surface machining of the metal frame to increase the adhesion of metal to ceramics. Adhesion of cobalt-chromium alloy and ceramics was investigated. A profilometer and a scanning electron microscope were used to analyze the morphology. To estimate the adhesion the shear strength was measured by the method based on ASTM D1002-10. A method of surface microrelief formation of metal samples by plasma-electrolyte treatment has been developed. Regimes for plasma-electrolyte surface treatment were investigated according to current-voltage characteristics and a surface roughness parameter. The samples were subjected to different surface machining techniques such as polishing, milling, sandblasting (so-called traditional methods), and plasma-electrolyte processing. Morphology of the surface for all samples was studied and the difference in microrelief was shown. The roughness and adhesive strength were measured for samples either. As a result, the mode for plasma- electrolytic surface treatment under which the adhesive strength was increased up to 183% (compared with the traditional methods) was found.     

Gene transfection of human mesenchymal stem cells with a nano‐hydroxyapatite–collagen scaffold containing DNA‐functionalized calcium phosphate nanoparticles

This study aimed to fabricate a growth factor‐releasing biodegradable scaffold for tissue regeneration. We prepared multishell calcium phosphate (CaP) nanoparticles functionalized with DNA, polyethyleneimine (PEI), protamine and octa‐arginine (R8) and compared their respective transfection activity and cell viability measures using human mesenchymal stem cells. DNA–protamine complexes improved the transfection efficiency of CaP nanoparticles with the exception of those functionalized with R8. These complexes also greatly reduced the cytotoxicity of PEI. In addition, we also fabricated DNA–protamine‐functionalized CaP nanoparticle‐loaded nano‐hydroxyapatite–collagen scaffolds and investigated their gene transfection efficiencies. These experiments showed that the scaffolds were associated with moderate hMSC cell viability and were capable of releasing the BMP‐2 protein into hMSCs following gene transfection. In particular, the scaffold loaded with protamine‐containing CaP nanoparticles showed the highest cell viability and transfection efficiency in hMSCs; thus, it might be suitable to serve as an efficient growth factor‐releasing scaffold.     

Bioactivation mechanisms of N-hydroxyaristolactams: Nitroreduction metabolites of aristolochic acids

Aristolochic acids (AAs) are human nephrotoxins and carcinogens found in concoctions of Aristolochia plants used in traditional medicinal practices worldwide. Genotoxicity of AAs is associated with the formation of active species catalyzed by metabolic enzymes, the full repertoire of which is unknown. Recently, we provided evidence that sulfonation is important for bioactivation of AAs. Here, we employ Salmonella typhimurium umu tester strains expressing human N-acetyltransferases (NATs) and sulfotransferases (SULTs), to study the role of conjugation reactions in the genotoxicities of N-hydroxyaristolactams (AL-I-NOH and AL-II-NOH), metabolites of AA-I and AA-II. Both N-hydroxyaristolactams show stronger genotoxic effects in umu strains expressing human NAT1 and NAT2, than in the parent strain. Additionally, AL-I-NOH displays increased genotoxicity in strains expressing human SULT1A1 and SULT1A2, whereas AL-II-NOH shows enhanced genotoxicity in SULT1A1/2 and SULT1A3 strains. 2,6-Dichloro-4-nitrophenol, SULTs inhibitor, reduced umuC gene expression induced by N-hydroxyaristolactams in SULT1A2 strain. N-hydroxyaristolactams are also mutagenic in parent strains, suggesting that an additional mechanism(s) may contribute to their genotoxicities. Accordingly, using putative SULT substrates and inhibitors, we found that cytosols obtained from human kidney HK-2 cells activate N-hydroxyaristolactams in aristolactam-DNA adducts with the limited involvement of SULTs. Removal of low-molecular-weight reactants in the 3.5–10 kDa range inhibits the formation of aristolactam-DNA by 500-fold, which could not be prevented by the addition of cofactors for SULTs and NATs. In conclusion, our results demonstrate that the genotoxicities of N-hydroxyaristolactams depend on the cell type and involve not only sulfonation but also N,O-acetyltransfer and an additional yet unknown mechanism(s). Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.