A Computed Tomography-Based Radiomic Prognostic Marker of Advanced High-Grade Serous Ovarian Cancer Recurrence: A Multicenter Study

Objectives: We used radiomic analysis to establish a radiomic signature based on preoperative contrast enhanced computed tomography (CT) and explore its effectiveness as a novel recurrence risk prognostic marker for advanced high-grade serous ovarian cancer (HGSOC).Methods: This study had a retrospective multicenter (two hospitals in China) design and a radiomic analysis was performed using contrast enhanced CT in advanced HGSOC (FIGO stage III or IV) patients. We used a minimum 18-month follow-up period for all patients (median 38.8 months, range 18.8–81.8 months). All patients were divided into three cohorts according to the timing of their surgery and hospital stay: training cohort (TC) and internal validation cohort (IVC) were from one hospital, and independent external validation cohort (IEVC) was from another hospital. A total of 620 3-D radiomic features were extracted and a Lasso-Cox regression was used for feature dimension reduction and determination of radiomic signature. Finally, we combined the radiomic signature with seven common clinical variables to develop a novel nomogram using a multivariable Cox proportional hazards model.Results: A final 142 advanced HGSOC patients were enrolled. Patients were successfully divided into two groups with statistically significant differences based on radiomic signature, consisting of four radiomic features (log-rank test P = 0.001, <0.001, <0.001 for TC, IVC, and IEVC, respectively). The discrimination accuracies of radiomic signature for predicting recurrence risk within 18 months were 82.4% (95% CI, 77.8–87.0%), 77.3% (95% CI, 74.4–80.2%), and 79.7% (95% CI, 73.8–85.6%) for TC, IVC, and IEVC, respectively. Further, the discrimination accuracies of radiomic signature for predicting recurrence risk within 3 years were 83.4% (95% CI, 77.3–89.6%), 82.0% (95% CI, 78.9–85.1%), and 70.0% (95% CI, 63.6–76.4%) for TC, IVC, and IEVC, respectively. Finally, the accuracy of radiomic nomogram for predicting 18-month and 3-year recurrence risks were 84.1% (95% CI, 80.5–87.7%) and 88.9% (95% CI, 85.8–92.5%), respectively.Conclusions: Radiomic signature and radiomic nomogram may be low-cost, non-invasive means for successfully predicting risk for postoperative advanced HGSOC recurrence before or during the perioperative period. Radiomic signature is a potential prognostic marker that may allow for individualized evaluation of patients with advanced HGSOC

Nanomaterial-Assisted Signal Enhancement of Hybridization for DNA Biosensors: A Review

Detection of DNA sequences has received broad attention due to its potential applications in a variety of fields. As sensitivity of DNA biosensors is determined by signal variation of hybridization events, the signal enhancement is of great significance for improving the sensitivity in DNA detection, which still remains a great challenge. Nanomaterials, which possess some unique chemical and physical properties caused by nanoscale effects, provide a new opportunity for developing novel nanomaterial-based signal-enhancers for DNA biosensors. In this review, recent progress concerning this field, including some newly-developed signal enhancement approaches using quantum-dots, carbon nanotubes and their composites reported by our group and other researchers are comprehensively summarized. Reports on signal enhancement of DNA biosensors by non-nanomaterials, such as enzymes and polymer reagents, are also reviewed for comparison. Furthermore, the prospects for developing DNA biosensors using nanomaterials as signal-enhancers in future are also indicated

Targeting centrosome amplification in aneuploid B-cell precursor acute lymphoblastic leukemia

B-cell precursor acute lymphoblastic leukemia (B-ALL) remains the single largest contributor to relapse in the pediatric leukemia patient population and new treatments are sorely needed to address this clinical challenge. Centrosomes play an important role in cell division, and centrosome abnormalities are a common feature in cancer cells. Mitotic cells with centrosome amplification are likely to form multipolar spindles, which generally lead to cell death. Cancer cells, therefore, must cluster supernumerary centrosomes to form pseudo-bipolar mitotic spindles and maintain cancer cell viability. My study investigates the efficacy of emerging inhibitors of centrosome clustering as new therapies to target pediatric B-ALL cells. As normal cells do not need to use centrosome clustering pathways, these inhibitors have the potential for low toxicity to healthy and growing tissues. However, tumor cells often resist targeted therapies and it is prudent to expect tumor adaption. My study shows that centrosome clustering inhibitors induce genetic and genomic instability in refractory leukemia cells, including micronuclei, which localize the DNA sensor cGAS and increase production of pro-inflammatory signals. Thus, refractory tumor cells may be immunogenic and activate an innate immune response. Overall, these findings identify centrosome clustering inhibitors as potential therapies to kill tumor cells and condition an immunogenic population that may be targeted by immune-based therapies to achieve long-term immune protection.Medicine, Faculty ofExperimental Medicine, Division ofMedicine, Department ofGraduat

miR-598 Represses Cell Migration and Invasion of Non-Small-Cell Lung Cancer by Inhibiting MSI2

Non-small-cell lung cancer (NSCLC) is one of the most frequent solid tumors and regarded as a significant threat to individual health around the world. MicroRNAs (miRs) are recognized as critical governors of gene expression during carcinogenesis, while their clinical significance and mechanism in NSCLC occurrence and development are required for further investigation. In this report, we characterized the functional role of miR-598 and its regulation mechanism in NSCLC. The expression level of miR-598 in NSCLC tissues and cell lines was detected by qRT-PCR. A549 cells were transiently transfected with miR-598 mimics or miR-598 inhibitors. Scratch assay and Transwell assay were used to detect cell transfection, migration, and invasion. Possible binding sites of miR-598 in MSI2 mRNA were predicted by bioinformatics and validated by dual-luciferase reporter gene system. The ability of migration and invasion was examined on cells transfected with MSI2 alone or cotransfected A549 cells with miR-598. The expression of miR-598 in NSCLC tissues was significantly lower than that in adjacent tissues, and the expression of miR-598 in NSCLC cell lines (A549, H1650, and H1299) was also significantly lower than that of normal lung epithelial cell line BEAS-2B. A549 cells were significantly inhibited in migration and invasion after transfection with miR-598 mimics, while miR-598 inhibitors were significantly enhanced in migration and invasion. MSI2 was a direct target gene of miR-598. MSI2 can promote the migration and invasion of A549 cells, but the ability to promote cell migration and invasion was reversed when miR-598 was introduced. In conclusion, miR-598 inhibits the migration and invasion of NSCLC by downregulating the target gene MSI2

A novel signature for predicting prognosis and immune landscape in cutaneous melanoma based on anoikis-related long non-coding RNAs

Abstract Anoikis is a unique form of apoptosis associated with vascularization and distant metastasis in cancer. Eliminating anoikis resistance in tumor cells could be a promising target for improving the prognosis of terminal cancer patients. However, current studies have not elaborated on the prognosis effect of anoikis-related long non-coding RNAs (lncRNAs) in cutaneous melanoma. Pre-processed data, including RNA sequences and clinical information, were retrieved from TCGA and GTEx databases. After a series of statistical analyses, anoikis-related lncRNAs with prognostic significance were identified, and a unique risk signature was constructed. Risk scores were further analyzed in relation to the tumor microenvironment, tumor immune dysfunction and exclusion, immune checkpoint genes, and RNA methylation genes. The indicators were also used to predict the potentially sensitive anti-cancer drugs. An anoikis-related lncRNAs risk signature consisting of LINC01711, POLH-AS1, MIR205HG, and LINC02416 was successfully established in cutaneous melanoma. Overall survival and progression-free survival of patients were strongly linked with the risk score, independently of other clinical factors. The low-risk group exhibited a more beneficial immunological profile, was less affected by RNA methylation, and was more sensitive to the majority of anti-cancer drugs, all of which indicated a better prognostic outcome. The 4 hub lncRNAs may be fundamental to studying the mechanism of anoikis in cutaneous melanoma and provide personalized therapy for salvaging drug resistance

A Simple Hydrophilic Palladium(II) Complex as a Highly Efficient Catalyst for Room Temperature Aerobic Suzuki Coupling Reactions in Aqueous Media

A study on room temperature Suzuki cross-coupling in an aqueous medium was carried out using a simple hydrophilic palladium (II) complex, trans-PdCl2(NH2CH2COOH)2 as catalyst in the presence of K2CO3 in air. This approach with a comparatively inexpensive and hydrophilic catalyst, mild reaction condition and aqueous media exhibits excellent catalytic activity towards the Suzuki coupling of aryl bromides and arylboronic acids, and good yields were obtained in the Suzuki coupling of activated aryl chlorides

Bipolar Argumentation Frameworks, Modal Logic and Semantic Paradoxes

Bipolar Argumentation Frameworks (BAF) are a natural extension of Dung’s Argumentation Frameworks (AF) where a relation of support between arguments is added to the standard attack relation. Despite their interest, BAF present several difficulties and their semantics are quite complex. This paper provides a definition of semantic concepts for BAF in terms of fixpoints of the functions of neutrality and defense, thus preserving most of the fundamental properties of Dung’s AF. From this angle it becomes easy to show that propositional dynamic logic provides an adequate language to talk about BAF. Finally, we illustrate how this framework allows to encode the structure of the referential discourse involved in semantic paradoxes such as the Liar. It turns out that such paradoxes can be seen as BAF without a stable extension

Anti-Inflammatory Effect of Dimethyl Fumarate Associates with the Inhibition of Thioredoxin Reductase 1 in RAW 264.7 Cells

Macrophages secrete a variety of pro-inflammatory cytokines in response to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) but abnormal release of cytokines unfortunately promotes cytokine storms. Dimethyl fumarate (DMF), an FDA-approved drug for multiple sclerosis (MS) treatment, has been found as an effective therapeutic agent for resolution. In this study, the anti-inflammatory effect of DMF was found to correlate to selenoprotein thioredoxin reductase 1 (TXNRD1). DMF irreversibly modified the Sec498 residue and C-terminal catalytic cysteine residues of TXNRD1 in a time- and dose-dependent manner. In LPS-stimulated RAW 264.7 cells, cellular TXNRD activity was increased through up-regulation of the protein level and DMF inhibited TXNRD activity and the nitric oxide (NO) production of RAW 264.7 cells. Meanwhile, the inhibition of TXNRD1 by DMF would contribute to the redox regulation of inflammation and promote the nuclear factor erythroid 2-related factor 2 (NRF2) activation. Notably, inhibition of cellular TXNRD1 by auranofin or TRi-1 showed anti-inflammatory effect in RAW 264.7 cells. This finding demonstrated that targeting TXNRD1 is a potential mechanism of using immunometabolites for dousing inflammation in response to pathogens and highlights the potential of TXNRD1 inhibitors in immune regulation