Ubiquitin E3 ligases in cancer: somatic mutation and amplification.

Defects in DNA double-strand break (DSB) repair signaling permit cancer cells to accumulate genomic alterations that confer their aggressive phenotype. Nevertheless, tumors depend on residual DNA repair abilities to survive the DNA damage induced by genotoxic stress. This is why only isolated DNA repair signaling is inactivated in cancer cells. DNA DSB repair signaling contributes to general mechanism for various types of lesions in diverse cell cycle phases. DNA DSB repair genes are frequently mutated and amplified in cancer; however, limited data exist regarding the overall genomic prospect and functional result of these modifications. We list the DNA repair genes and related E3 ligases. Mutation and expression frequencies of these genes were analyzed in COSMIC and TCGA. The 11 genes with a high frequency of mutation differed between cancers, and mutations in many DNA DSB repair E3 ligase genes were related to a higher total mutation burden. DNA DSB repair E3 ligase genes are involved in tumor suppressive or oncogenic functions, such as RNF168 and FBXW7, by assisting the functionality of these genomic alterations. DNA damage response-related E3 ligases, such as RNF168, FBXW7, and HERC2, were generated with more than 10% mutation in several cancer cells. This study provides a broad list of candidate genes as potential biomarkers for genomic instability and novel therapeutic targets in cancer. As a DSB related proteins considerably appear the possibilities for targeting DNA repair defective tumors or hyperactive DNA repair tumors. Based on recent research, we describe the relationship between unstable DSB repairs and DSB-related E3 ligases. [BMB Reports 2023; 56(5): 265-274].

Prone position [18F]FDG PET/CT to reduce respiratory motion artefacts in the evaluation of lung nodules.

OBJECTIVES: 2-Deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron-emission tomography/computed tomography (PET/CT) is widely used to evaluate lung nodules, although respiratory motion artefacts may occur. We investigated the value of prone position PET/CT (pPET/CT) in lung nodule evaluation compared with standard supine position PET/CT (sPET/CT). METHODS: We retrospectively reviewed 28 consecutive patients (20 men; age, 65.6 ± 12.1 years) with a lung nodule (size, 16.8 ± 5.5 mm) located below the sub-carinal level who underwent [18F]FDG PET/CT in a standard supine position and additional prone position. The maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV), difference of diaphragm position between PET and CT (DDP), Dice's similarity coefficient (DSC) and occurrence of mis-registration were analysed. The [18F]FDG uptake of 20 biopsy-confirmed (15 malignant) nodules was evaluated visually. RESULTS: pPET/CT yielded a significantly higher SUVmax, lower MTV and shorter DDP than with sPET/CT (p = 0.043, 0.007 and 0.021, respectively). Mis-registration occurred in 53.6% of cases in sPET/CT and in 28.6% of cases in pPET/CT (p = 0.092). Among the 15 patients with mis-registration in sPET/CT, 10 patients (66.7%) did not show mis-registration in pPET/CT. DSC was higher in pPET/CT than in sPET/CT in 18 out of 28 patients (64.3%). In visual analysis, malignant nodules exhibited a higher [18F]FDG uptake positivity than benign nodules in pPET/CT (93.3% vs. 40.0%, p = 0.032) but not in sPET/CT (80.0% vs. 40.0%, p = 0.131). CONCLUSIONS: pPET/CT reduces respiratory motion artefact and enables more-precise measurements of PET parameters. KEY POINTS: • In prone position PET/CT, the decrease in the blurring effect caused by reduced respiratory motion resulted in a higher SUVmax and lower MTV in lung nodules than that with supine position PET/CT. • Prone position PET/CT was useful to interpret correctly malignant lung nodules as being positive in individual cases that had a negative result in supine position PET/CT.

Ileocolic Intussusception Accompanied with Inflamed Appendix: 2 Case Reports.

Intussusception and acute appendicitis are common emergency conditions in children. They should be promptly differentiated in pediatric patients presenting with suggestive symptoms. However, both diseases may occur simultaneously. Herein, we present two cases of intussusception of the appendix accompanied with appendicitis.

Right hydronephrosis as a sign of complicated appendicitis.

OBJECTIVE: Acute appendicitis is known for one of the most common cause of acute abdomen. However, it is still challenging to clearly distinguish complicated from uncomplicated appendicitis preoperatively. We investigated the association between right hydronephrosis and complicated appendicitis compared with other computed tomography (CT) findings of acute appendicitis. MATERIALS AND METHODS: 1275 patients who pathologically diagnosed with acute appendicitis were included. They were classified into the complicated appendicitis and uncomplicated appendicitis groups based on their histopathological results. We reviewed their CT findings, including right hydronephrosis, appendiceal wall defect, periappendiceal abscess, extraluminal or intraluminal free air, appendicolith, appendiceal dilatation, appendiceal wall thickening, periappendiceal infiltration, periappendiceal fluid collection, and ascites. Comparison between the two groups was performed and the diagnostic performance of each CT finding was evaluated. The location of appendix and periureteral extension of periappendiceal infiltration were evaluated in patients with right hydronephrosis. RESULTS: Out of 1275 patients, 29 (2.3 %) patients showed right hydronephrosis. Right hydronephrosis was significantly related to complicated appendicitis with the odds ratio of 4.90 (95 % confidence interval, 1.62-14.83; P = 0.005). Right hydronephrosis yielded specificity of 99.3 %. All patients with right hydronephrosis accompanied with periappendiceal infiltration and 28 (96.6 %) patients showed periureteral extension. Subcecal and pelvic areas are the most common locations, with 11 (37.9 %) patients each. CONCLUSION: The presence of right hydronephrosis was specific finding for complicated appendicitis and it could be considered as one of indirect sign of complicated appendicitis.

Clinical and Radiologic Findings of COVID-19 Pneumonia: South Korean Experience From Three Cases.

Coronavirus disease 2019 (COVID-19) is spreading rapidly around the world. Several articles have so far reported on radiological findings of COVID-19 pneumonia. Herein, we present three cases of COVID-19 pneumonia in South Korea, and provide clinical information as well as chest radiograph and chest CT findings.

A Newly Isolated Bacteriophage, PBES 02, Infecting Cronobacter sakazakii.

A novel bacteriophage, PBES 02, infecting Cronobacter sakazakii was isolated and characterized. It has a spherical head of 90 nm in diameter and a tail of 130 nm in length, and belongs to Myoviridae as observed under a transmission electron microscope. The major virion protein appears to be 38 kilodaltons (kDa) in size. The latent period of PBES 02 is 30 min and the burst size is 250. Infectivity of the phage remained intact after exposure to temperatures ranging from 4°C to 55°C for 1 h. It was also stable after exposure to pHs ranging from 6 to 10 for 1 h. The phage effectively removed contaminating Cronobacter sakazakii from broth infant formula. PBES 02 has a double-stranded DNA genome of 149,732 bases. Its GC ratio is 50.7%. Sequence analysis revealed that PBES 02 has 299 open reading frames (ORFs) and 14 tRNA genes. Thirty-nine ORFs were annotated, including 24 related to replication and regulation functions, 10 related to structural proteins, and 5 related to DNA packaging. The genome of PBES 02 is closely related to that of two other C. sakazakii phages, CR3 and CR8. Comparison of DNA sequences of genes encoding the major capsid protein revealed a wide geographical distribution of related phages over Asia, Europe, and America.

The efficacy of TachoComb on reducing postoperative complications after tonsillectomy in children.

OBJECTIVE: A fibrinogen/thrombin-based collagen fleece (TachoComb) is a powerful topical hemostatic agent that has been widely used in various surgical specialties with a favorable outcome. The purpose of this study was to investigate the effect of TachoComb application on postoperative complications after tonsillectomy. MATERIALS AND METHODS: A total of 1633 children had undergone tonsillectomy with or without adenoidectomy were included in this study. After removal of both tonsils, 1057 patients (64.7%) were treated with TachoComb on the tonsillectomy site and 576 without TachoComb. Post-tonsillectomy pain, hemorrhage rates, re-admission rates, and emergency surgery rates for post-tonsillectomy hemorrhage were evaluated between patients who received TachoComb and those who did not. RESULTS: TachoComb treatment significantly reduced post-tonsillectomy pain and emergency surgery rates for post-tonsillectomy hemorrhage. However, postoperative hemorrhage rate and re-admission rates for post-tonsillectomy hemorrhage were not statistically significant between TachoComb treatment group and control group. No patients had complications or adverse reactions after TachoComb treatment. CONCLUSIONS: The use of TachoComb after tonsillectomy significantly reduces pain and emergency surgery for severe post-tonsillectomy hemorrhage without an apparent adverse effect. Therefore, TachoComb may be a useful adjuvant in terms of efficacy and safety after tonsillectomy.

Structural insights of the nucleotide-dependent conformational changes of Thermotoga maritima MutL using small-angle X-ray scattering analysis.

MutL is required to assist the mismatch repair protein MutS during initiation of the methyl-directed mismatch repair (MMR) response in various organisms ranging from prokaryotes to eukaryotes. Despite this necessity, the inherent propensity of MutL to aggregate has led to significant difficulties in determining its biological relationship with other MMR-related proteins. Here, we perform analysis on the thermostable MutL protein found in Thermotoga maritima MSB8 (TmL). Size exclusion chromatographic analysis indicates the lack of aggregated forms with the exception of a dimeric TmL. Small-angle X-ray scattering (SAXS) analysis reveals that the solution structures of the full-length TmL and its corresponding complexes with nucleotides and ssDNA undergo conformational changes. The elucidated TmL SAXS model is superimposed to the crystal structure of the C-terminal domain of Escherichia coli MutL. In addition, the N-terminal SAXS model of TmL exists as monomeric form, indicating that TmL has a structurally flexible N-terminal domain. TmL SAXS analysis can suggest a considerable possibility on a new 3D view of the previously unresolved full-length MutL molecule.