Search

Oxygen and nutrient deprivation are common features of solid tumors. Although abnormal alternative splicing (AS) has been found to be an important driving force in tumor pathogenesis and progression, the regulatory mechanisms of AS that underly the adaptation of cancer cells to harsh microenvironments remain unclear. Here, we found that hypoxia- and nutrient deprivation-induced asparagine endopeptidase (AEP) specifically cleaved DDX3X in a HIF1A-dependent manner. This cleavage yields truncated carboxyl-terminal DDX3X (tDDX3X-C), which translocates and aggregates in the nucleus. Unlike intact DDX3X, nuclear tDDX3X-C complexes with an array of splicing factors and induces AS events of many premRNAs; for example, enhanced exon skipping (ES) in exon 2 of the classic tumor suppressor PRDM2 leads to a frameshift mutation of PRDM2. Intriguingly, the isoform ARRB1-[DELTA]exon 13 binds to glycolytic enzymes and regulates glycolysis. By utilizing in vitro assays, glioblastoma organoids, and animal models, we revealed that AEP/tDDX3X-C promoted tumor malignancy via these isoforms. More importantly, high AEP/tDDX3X-C/ARRB1- [DELTA]exon 13 in cancerous tissues was tightly associated with poor patient prognosis. Overall, our discovery of the effect of AEP-cleaved DDX3X switching on alternative RNA splicing events identifies a mechanism in which cancer cells adapt to oxygen and nutrient shortages and provides potential diagnostic and/or therapeutic targets., Introduction In the tumor microenvironment, cells often face a certain degree of oxygen and nutrient deprivation. Cancer cells strive to survive and proliferate in this harsh environment in multiple ways, [...]

The programmed cell death 4 (PDCD4) tumor-suppressor gene regulates cell apoptosis, protein translation, signal transduction, and induction of mediators of inflammation. However, the mechanism by which PDCD4 is down-regulated and regulates tumor growth remains elusive. In this study, we showed that PDCD4 is down-regulated in glioma cells and acts as a tumor suppressor. Based on the TCGA data, we confirmed that AKT2, but not AKT1 or AKT3, interacts with PDCD4, thus leading to the suppression of PDCD4 in glioma cells. Moreover, the analysis suggested that PDCD4 regulates the expression of IL-5, CCL-5, VEGF, and CXCL10 via the NF-kB pathway. Additionally, depletion of levels of PDCD4 promoted angiogenic activity of glioma cells via the VEGF-STAT3 pathway. When tumor cells over-expressing PDCD4 were injected into nude mice, the increased expression of PDCD4 blocked tumorigenesis and prolonged overall survival. Our study indicates the need to develop drugs that can modulate the expression of PDCD4 and test their efficacy in clinical trials.

Background: Protein p62 (sequestosome 1) encoded by gene SQSTM1 plays a vital role in mediating protectively selective autophagy in tumor cells under stressed conditions. CircSQSTM1 (hsa_circ_0075323) is a circular transcript generated from gene SQSTM1 (chr5:179260586–179260782) by back-splicing. However, the potential role of hsa_hsa_circ_0075323 in glioblastoma (GBM) remains unclear. Here, we aimed to explore the biological function of hsa_circ_0075323 in GBM and its relationship with autophagy regulation. Results: Hsa_circ_0075323 is highly expressed in GBM cells and mainly locates in the cytoplasm. Inhibition of hsa_circ_0075323 in U87-MG and T98G cells attenuated proliferation and invasion ability significantly, while upregulation of has_ circ_0075323 enhanced proliferation and migration of U251-MG and A172 cells. Mechanistically, depletion of hsa_circ_0075323 in GBM cells resulted in impaired autophagy, as indicated by increased expression of p62 and decreased expression of LC3B. Conclusions: Hsa_circ_0075323 regulates p62-mediated autophagy pathway to promote GBM progression and may serve as a prognostic biomarker potentially. [ABSTRACT FROM AUTHOR]

Introduction: To explore and evaluate the performance of MRI‐based brain tumor super‐resolution generative adversarial network (MRBT‐SR‐GAN) for improving the MRI image resolution in brain tumors. Methods: A total of 237 patients from December 2018 and April 2020 with T2‐fluid attenuated inversion recovery (FLAIR) MR images (one image per patient) were included in the present research to form the super‐resolution MR dataset. The MRBT‐SR‐GAN was modified from the enhanced super‐resolution generative adversarial networks (ESRGAN) architecture, which could effectively recover high‐resolution MRI images while retaining the quality of the images. The T2‐FLAIR images from the brain tumor segmentation (BRATS) dataset were used to evaluate the performance of MRBT‐SR‐GAN contributed to the BRATS task. Results: The super‐resolution T2‐FLAIR images yielded a 0.062 dice ratio improvement from 0.724 to 0.786 compared with the original low‐resolution T2‐FLAIR images, indicating the robustness of MRBT‐SR‐GAN in providing more substantial supervision for intensity consistency and texture recovery of the MRI images. The MRBT‐SR‐GAN was also modified and generalized to perform slice interpolation and other tasks. Conclusions: MRBT‐SR‐GAN exhibited great potential in the early detection and accurate evaluation of the recurrence and prognosis of brain tumors, which could be employed in brain tumor surgery planning and navigation. In addition, this technique renders precise radiotherapy possible. The design paradigm of the MRBT‐SR‐GAN neural network may be applied for medical image super‐resolution in other diseases with different modalities as well. [ABSTRACT FROM AUTHOR]

Non–small-cell lung cancer (NSCLC) is one of the most fatal malignant tumors harmful to human health. Previous studies report that Platycodin D (PD) exhibits anti-tumor effects in multiple human cancers, including NSCLC, but the underlying mechanisms are largely unknown. Accumulating evidence indicates that non-coding RNAs (ncRNAs) participate in NSCLC disease progression, but the link between PD and the ncRNAs in NSCLC is poorly elucidated. Here, we used whole transcriptome sequencing to systematically investigate the RNAs-associated regulatory network in the PD treating NSCLC cell lines. A total of 942 significantly dysregulated RNAs were obtained. Among those, five circRNAs and six IncRNAs were rigorously selected via database and in vitro validation. In addition, the functional enrichment study of differentially expressed mRNAs, single nucleotide polymorphisms (SNPs) within PD-related mRNA structures, and the interaction between PD and mRNA-related proteins were analyzed through gene set enrichment analysis (GSEA), structural variant analysis, and molecular docking, respectively. With further in vitro validation, the results show that PD inhibits cell proliferation, arrests the cell cycle, and induces cell apoptosis through targeting BCL2-related proteins. We hope these data can provide a full concept of PD-related molecular changes, leading to a new treatment for NSCLC. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to establish a nomogram model for predicting the risk of short-term recurrence in glioma patients. Methods: The clinical data of recurrent glioma patients were summarized and analyzed in this study. Univariate and multivariate logistic regression analyses were performed to analyze the correlation between clinical data and the risk of short-term recurrence after operation. A nomogram was established based on the multivariate logistic regression model results. Results: A total of 175 patients with recurrent glioma were enrolled, with 53 patients in the short-term recurrence (STR) group (recurrent time ≤6 months) and 122 patients in the long-term recurrence (LTR) group (recurrent time ≥36 months). Univariate analysis revealed that age at diagnosis, Karnofsky performance scores (KPSs), tumor location, glioma grade, glioma type, extent of resection (EOR), adjuvant chemotherapy (ad-CT), concurrent chemotherapy (co-CT), and isocitrate dehydrogenase (IDH) status were significantly associated with the short-term glioma recurrence. Multivariate analyses revealed that age at diagnosis, KPS, glioma grade, EOR, and IDH were independent risk factors for short-term glioma recurrence. A risk nomogram for the short-term recurrence of glioma was established, with the concordance index (C-index) of 0.971. The findings of calibration and receiver operating characteristic (ROC) curves showed that our nomogram model had good performance and discrimination to estimate short-term recurrence probability. Conclusion: This nomogram model provides reliable information about the risk of short-term glioma recurrence for oncologists and neurosurgeons. This model can predict the short-term recurrence probability and give assistance to decide the interval of follow-up or formulate individualized treatment strategies based on the predicted results. A free online prediction risk tool for this nomogram is provided: https://rj2021.shinyapps.io/Nomogram%5f recurrence-risk/. [ABSTRACT FROM AUTHOR]

Objectives: Endoscopic nasopharyngectomy (ENPG) is a promising way in treating recurrent nasopharyngeal carcinoma (rNPC), but sometimes may require therapeutic internal carotid artery (ICA) occlusion beforehand. Balloon test occlusion (BTO) is performed to evaluate cerebral ischemic tolerance for ICA sacrifice. However, absence of neurological deficits during BTO does not preclude occur of delayed cerebral ischemia after permanent ICA occlusion. In this study, we evaluate the utility of near-infrared spectroscopy (NIRS) regional cerebral oxygen saturation (rSO2) monitoring during ICA BTO to quantify cerebral ischemic tolerance and to identify the valid cut-off values for safe carotid artery occlusion. This study also aims to find out angiographic findings of cerebral collateral circulation to predict ICA BTO results simultaneously. Material and Methods: 87 BTO of ICA were performed from November 2018 to November 2020 at authors' institution. 79 angiographies of collateral flow were performed in time during BTO and classified into several Subgroups and Types according to their anatomic and collateral flow configurations. 62 of 87 cases accepted monitoring of cerebral rSO2. Categorical variables were compared by using Fisher exact tests and Mann–Whitney U tests. Receiver operating characteristic curve analysis was used to determine the most suitable cut-off value. Results: The most suitable cut-off △rSO2 value for detecting BTO-positive group obtained through ROC curve analysis was 5% (sensitivity: 100%, specificity: 86%). NIRS rSO2 monitoring wasn't able to detect BTO false‐negative results (p = 0.310). The anterior Circle was functionally much more important than the posterior Circle among the primary collateral pathways. The presence of secondary collateral pathways was considered as a sign of deteriorated cerebral hemodynamic condition during ICA BTO. In Types 5 and 6, reverse blood flow to the ICA during BTO protected patients from delayed cerebral ischemia after therapeutic ICA occlusion (p = 0.0357). In Subgroup IV, absence of the posterior Circle was significantly associated with BTO-positive results (p = 0.0426). Conclusion: Angiography of cerebral collateral circulation during ICA BTO is significantly correlated with ICA BTO results. Angiographic ICA BTO can be performed in conjunction with NIRS cerebral oximeter for its advantage of being noninvasive, real-time, cost-effective, simple for operation and most importantly for its correct prediction of most rSO2 outcomes of ICA sacrifice. However, in order to ensure a safe carotid artery occlusion, more quantitative adjunctive blood flow measurements are recommended when angiography of cerebral collateral circulation doesn't fully support rSO2 outcome among clinically ICA BTO-negative cases. [ABSTRACT FROM AUTHOR]

Background: Isocitrate dehydrogenase wild-type (WT) glioblastoma (GBM) accounts for 90% of all GBMs, yet only 27% of isocitrate dehydrogenase WT-GBMs have p53 mutations. However, the tumor surveillance function of WT-p53 in GBM is subverted by mechanisms that are not fully understood.Methods: We investigated the proteolytic inactivation of WT-p53 by asparaginyl endopeptidase (AEP) and its effects on GBM progression in cancer cells, murine models, and patients' specimens using biochemical and functional assays. The sera of healthy donors (n = 48) and GBM patients (n = 20) were examined by enzyme-linked immunosorbent assay. Furthermore, effects of AEP inhibitors on GBM progression were evaluated in murine models (n = 6-8 per group). The statistical significance between groups was determined using two-tailed Student t tests.Results: We demonstrate that AEP binds to and directly cleaves WT-p53, resulting in the inhibition of WT-p53-mediated tumor suppressor function in both tumor cells and stromal cells via extracellular vesicle communication. High expression of uncleavable p53-N311A-mutant rescue AEP-induced tumorigenesis, proliferation, and anti-apoptotic abilities. Knock down or pharmacological inhibition of AEP reduced tumorigenesis and prolonged survival in murine models. However, overexpression of AEP promoted tumorigenesis and shortened the survival time. Moreover, high AEP levels in GBM tissues were associated with a poor prognosis of GBM patients (n = 83; hazard ratio = 3.94, 95% confidence interval = 1.87 to 8.28; P < .001). A correlation was found between high plasma AEP levels and a larger tumor size in GBM patients (r = 0.6, P = .03), which decreased dramatically after surgery.Conclusions: Our results indicate that AEP promotes GBM progression via inactivation of WT-p53 and may serve as a prognostic and therapeutic target for GBM. [ABSTRACT FROM AUTHOR]

Byline: Liemei. Guo, Chunlong. Zhong, Jiyao. Jiang, Yongming. Qiu Sir, A 74-year-old man presented with a 2-week history of decreased sensation and weakness of bilateral lower extremities along with urinary [...]

Byline: Zhaofeng. Lu, Gangyi. Zhu, Yongming. Qiu, Xiaobing. Cheng Aims: To investigate the therapeutic effect of minimally-invasive aspiration and drainage in traumatic epidural hematoma straddling transverse sinus (TEHSTS). Materials and [...]

Byline: Liemei. Guo, Yongming. Qiu Sir, A 45-year-old male was admitted with headache and vomiting of one-day duration. Physical examination revealed neck stiffness. Cranial computed tomography (CT) scan showed subarachnoid [...]

Byline: Liemei. Guo, Yongming. Qiu, Jianwei. Ge, Xiaohua. Zhang Sir, A 50-year-old female presented with severe headache of 20 h duration. Neurological examination was unremarkable except for neck stiffness. Cranial [...]

Byline: Jiong. Dai, Shanquan. Li, Xiaoxiong. Li, Wenhao. Xiong, Yongming. Qiu Background : Intraventricular hemorrhage (IVH) is an independent risk factor for both morbidity and mortality in patients with intracerebral [...]