ABSTRACT
BACKGROUND: In assessing the clinical utility and safety of 3.0 T intraoperative magnetic resonance imaging (iMRI) combined with multimodality functional MRI (fMRI) guidance in the resection of functional area gliomas, we conducted a study. METHOD: Among 120 patients with newly diagnosed functional area gliomas who underwent surgical treatment, 60 were included in each group: the integrated group with iMRI and fMRI and the conventional navigation group. Between-group comparisons were made for the extent of resection (EOR), preoperative and postoperative activities of daily living based on the Karnofsky performance status, surgery duration, and postoperative intracranial infection rate. RESULTS: Compared to the conventional navigation group, the integrated navigation group with iMRI and fMRI exhibited significant improvements in tumor resection (complete resection rate: 85.0% vs. 60.0%, P = 0.006) and postoperative life self-care ability scores (Karnofsky score) (median ± interquartile range: 90 ± 25 vs. 80 ± 30, P = 0.013). Additionally, although the integrated navigation group with iMRI and fMRI required significantly longer surgeries than the conventional navigation group (mean ± standard deviation: 411.42 ± 126.4 min vs. 295.97 ± 96.48 min, P<0.0001), there was no significant between-group difference in the overall incidence of postoperative intracranial infection (16.7% vs. 18.3%, P = 0.624). CONCLUSION: The combination of 3.0 T iMRI with multimodal fMRI guidance enables effective tumor resection with minimal neurological damage.
Subject(s)
Brain Neoplasms , Glioma , Magnetic Resonance Imaging , Humans , Male , Female , Brain Neoplasms/surgery , Brain Neoplasms/diagnostic imaging , Glioma/surgery , Glioma/diagnostic imaging , Middle Aged , Magnetic Resonance Imaging/methods , Adult , Aged , Retrospective Studies , Surgery, Computer-Assisted/methods , Neuronavigation/methods , Treatment Outcome , Monitoring, Intraoperative/methods , Neurosurgical Procedures/methodsABSTRACT
Introduction: Glioblastoma multiforme (GBM), the most common primary malignant brain tumor, is notorious for its aggressive growth and dismal prognosis. This study aimed to elucidate the molecular underpinnings of GBM, particularly focusing on the role of AGBL4 and its connection to inflammatory pathways, to discover viable therapeutic targets. Methods: Single-cell sequencing was utilized to examine the expression levels of AGBL4 and functional assays were performed to assess the effects of AGBL4 modulation. Results: Our findings identified the significant upregulation of AGBL4 in GBM, which correlated with adverse clinical outcomes. Functional assays demonstrated that AGBL4 knockdown inhibited GBM cell proliferation, migration, and invasion and influenced inflammatory response pathways, while AGBL4 overexpression promoted these activities. Further investigation revealed that AGBL4 exerted its oncogenic effects through modulation of MMP-1, establishing a novel regulatory axis critical for GBM progression and inflammation. Discussion: Both AGBL4 and MMP-1 may be pivotal molecular targets, offering new avenues for targeted therapy in GBM management.
Subject(s)
Brain Neoplasms , Glioblastoma , Matrix Metalloproteinase 1 , Glioblastoma/pathology , Glioblastoma/metabolism , Glioblastoma/genetics , Humans , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 1/genetics , Brain Neoplasms/pathology , Brain Neoplasms/metabolism , Brain Neoplasms/genetics , Brain Neoplasms/immunology , Cell Line, Tumor , Cell Proliferation , Cell Movement/genetics , Disease Progression , Inflammation/metabolism , Gene Expression Regulation, Neoplastic , Signal Transduction , MaleABSTRACT
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 pre-mRNAs; 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-Δexon 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-Δexon 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.
Subject(s)
Alternative Splicing , Glioblastoma , Animals , Humans , DEAD-box RNA Helicases/genetics , DEAD-box RNA Helicases/metabolism , Glioblastoma/pathology , Oxygen/metabolism , Protein Isoforms/metabolism , RNA Splicing , RNA Splicing Factors/metabolism , Tumor MicroenvironmentABSTRACT
BACKGROUND: Abnormal proliferation and migration of cells are hallmarks of cancer initiation and malignancy. Asparagine endopeptidase (AEP) has specific substrate cleavage ability and plays a pro-cancer role in a variety of cancers. However, the underlying mechanism of AEP in cancer proliferation and migration still remains unclear. METHODS: Co-immunoprecipitation and following mass spectrometry were used to identify the substrate of AEP. Western blotting was applied to measure the expression of proteins. Single cell/nuclear-sequences were done to detect the heterogeneous expression of Tmod3 in tumor tissues. CCK-8 assay, flow cytometry assays, colony formation assay, Transwell assay and scratch wound-healing assay were performed as cellular functional experiments. Mouse intracranial xenograft tumors were studied in in vivo experiments. RESULTS: Here we showed that AEP cleaved a ubiquitous cytoskeleton regulatory protein, tropomodulin-3 (Tmod3) at asparagine 157 (N157) and produced two functional truncations (tTmod3-N and tTmod3-C). Truncated Tmod3 was detected in diverse tumors and was found to be associated with poor prognosis of high-grade glioma. Functional studies showed that tTmod3-N and tTmod3-C enhanced cancer cell migration and proliferation, respectively. Animal models further revealed the tumor-promoting effects of AEP truncated Tmod3 in vivo. Mechanistically, tTmod3-N was enriched in the cell cortex and competitively inhibited the pointed-end capping effect of wild-type Tmod3 on filamentous actin (F-actin), leading to actin remodeling. tTmod3-C translocated to the nucleus, where it interacted with Staphylococcal Nuclease And Tudor Domain Containing 1 (SND1), facilitating the transcription of Ras Homolog Family Member A/Cyclin Dependent Kinases (RhoA/CDKs). CONCLUSION: The newly identified AEP-Tmod3 protease signaling axis is a novel "dual-regulation" mechanism of tumor cell proliferation and migration. Our work provides new clues to the underlying mechanisms of cancer proliferation and invasive progression and evidence for targeting AEP or Tmod3 for therapy.
Subject(s)
Actins , Brain Neoplasms , Cysteine Endopeptidases , Endonucleases , Glioma , Tropomodulin , rhoA GTP-Binding Protein , Actins/metabolism , Animals , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Cyclin-Dependent Kinases/metabolism , Cysteine Endopeptidases/metabolism , Cytoskeletal Proteins , Endonucleases/metabolism , Glioma/metabolism , Glioma/pathology , Heterografts , Humans , Mice , Signal Transduction , Tropomodulin/metabolism , rhoA GTP-Binding Protein/metabolismABSTRACT
BACKGROUND: Glioblastoma (GBM) is a prevalent brain malignancy with an extremely poor prognosis, which is attributable to its invasive biological behavior. The RNA-binding motif protein 8A (RBM8A) has different effects on various human cancers. However, the role of RBM8A in GBM progression remains unclear. METHODS: We investigated the expression levels of RBM8A in 94 GBM patients and explored the correlation between RBM8A expression and patient prognosis. Using in vitro and in vivo assays, combined with GBM sequencing data from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we examined whether and how RBM8A contributes to GBM progression. RESULTS: RBM8A was up-regulated in GBM tissues, and its higher expression correlated with worse prognosis. Knockdown of RBM8A inhibited GBM progression and invasion ability both in vitro and in vivo. On the contrary, overexpression of RBM8A promoted GBM progression and invasion ability. Enrichment analysis of differentially expressed genes in GBM data identified the Notch1/STAT3 network as a potential downstream target of RBM8A, and this was supported by molecular docking studies. Furthermore, we demonstrated that RBM8A regulates the transcriptional activity of CBF1. The γ-secretase inhibitor DAPT significantly reversed RBM8A-enhanced GBM cell proliferation and invasion, and was associated with down-regulation of p-STAT3 and Notch1 protein. Finally, the gene set variance analysis score of genes involved in regulation of the Notch1/STAT3 network by RBM8A showed good diagnostic and prognostic value for GBM. CONCLUSIONS: RBM8A may promote GBM cell proliferation and migration by activating the Notch/STAT3 pathway in GBM cells, suggesting that RBM8A may serve as a potential therapeutic target for the treatment of GBM.
ABSTRACT
ABSTRACT: Chordoid glioma is a rare low-grade tumor that originates almost exclusively in the anterior part of the third ventricle. The diagnosis and treatment of the tumor remain controversial. In this article, the authors present a novel case of chordoid glioma of the third ventricle. The patient was treated with less invasive microsurgery followed by low-dose gamma knife radiosurgery. Magnetic resonance imaging revealed a decrease in tumor size and necrosis in the central region of the tumor, without significant complications at follow-up 14 months later. Based on these findings, the authors suggest that less invasive microsurgical resection followed by low-dose gamma knife radiosurgery is safe and effective for the treatment of chordoid glioma of the third ventricle.
Subject(s)
Cerebral Ventricle Neoplasms , Glioma , Radiosurgery , Third Ventricle , Cerebral Ventricle Neoplasms/diagnostic imaging , Cerebral Ventricle Neoplasms/surgery , Glioma/diagnostic imaging , Glioma/surgery , Humans , Magnetic Resonance Imaging , Third Ventricle/diagnostic imaging , Third Ventricle/surgeryABSTRACT
The enhancer of zeste homologue 2 (EZH2) is a histone H3 lysine 27 methyltransferase that promotes tumorigenesis in a variety of human malignancies by altering the expression of tumour suppressor genes. To evaluate the prognostic value of EZH2 in glioma, we analysed gene expression data and corresponding clinicopathological information from the Chinese Glioma Genome Atlas, the Cancer Genome Atlas and GTEx. Increased expression of EZH2 was significantly associated with clinicopathologic characteristics and overall survival as evaluated by univariate and multivariate Cox regression. Gene Set Enrichment Analysis revealed an association of EZH2 expression with the cell cycle, DNA replication, mismatch repair, p53 signalling and pyrimidine metabolism. We constructed a nomogram for prognosis prediction with EZH2, clinicopathologic variables and significantly correlated genes. EZH2 was demonstrated to be significantly associated with several immune checkpoints and tumour-infiltrating lymphocytes. Furthermore, the ESTIMATE and Timer Database scores indicated correlation of EZH2 expression with a more immunosuppressive microenvironment for glioblastoma than for low grade glioma. Overall, our study demonstrates that expression of EZH2 is a potential prognostic molecular marker of poor survival in glioma and identifies signalling pathways and immune checkpoints regulated by EHZ2, suggesting a direction for future application of immune therapy in glioma.
Subject(s)
Brain Neoplasms/metabolism , Enhancer of Zeste Homolog 2 Protein/metabolism , Glioma/metabolism , Brain Neoplasms/genetics , Brain Neoplasms/immunology , Brain Neoplasms/pathology , Cell Line, Tumor , Enhancer of Zeste Homolog 2 Protein/genetics , Gene Expression Regulation, Neoplastic , Glioma/genetics , Glioma/immunology , Glioma/pathology , Humans , Immunity , Nomograms , Prognosis , Signal Transduction/genetics , Survival Analysis , Tumor Microenvironment/geneticsABSTRACT
Pseudogenes, which are long noncoding RNAs that originate from protein-coding genes, have been suggested to play important roles in disease. Although studies have revealed high expression of legumain (LGMN) in many types of tumors, the regulation of LGMN remains largely unknown. Here, we found that a novel LGMN pseudogene (LGMNP1) was upregulated in glioblastoma (GBM) tissues and high LGMNP1 expression in GBM cells enhanced proliferation and invasion. Biochemical analysis showed that cytoplasmic LGMNP1 functionally targeted miR-495-3p in a manner involving an RNA-induced silencing complex. Dual-luciferase reporter assays demonstrated that LGMN was a target of miR-495-3p, and LGMN was upregulated and positively correlated with LGMNP1 in GBM. Moreover, miR-495-3p was downregulated and negatively correlated with LGMNP1 in GBM tissues. Notably, the tumor-promoting effects of LGMNP1 upregulation could be alleviated by miR-495-3p mimics. Furthermore, GBM cells overexpressing LGMNP1 exhibited more aggressive tumor progression and elevated LGMN expression in vivo. Thus, our data illustrate that LGMNP1 exerts its oncogenic activity, at least in part, as a competitive endogenous RNA (ceRNA) that elevates LGMN expression by sponging miR-495-3p. CeRNA-mediated miRNA sequestration might be a novel therapeutic strategy in GBM.
Subject(s)
Brain Neoplasms/pathology , Cysteine Endopeptidases/genetics , Gene Expression Regulation, Neoplastic/genetics , Glioblastoma/pathology , MicroRNAs/metabolism , Animals , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Cysteine Endopeptidases/metabolism , Disease Progression , Glioblastoma/genetics , Glioblastoma/metabolism , Heterografts , Humans , Mice , Mice, Nude , Pseudogenes/genetics , RNA, Long Noncoding/geneticsABSTRACT
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.
Subject(s)
Cysteine Endopeptidases/metabolism , Glioblastoma/metabolism , Tumor Suppressor Protein p53/metabolism , Animals , Cell Line, Tumor , Cysteine Proteinase Inhibitors/pharmacology , Disease Progression , Glioblastoma/enzymology , Glioblastoma/pathology , Heterografts , Human Umbilical Vein Endothelial Cells , Humans , Mice , Mice, Transgenic , Stromal Cells/enzymology , Stromal Cells/metabolism , Stromal Cells/pathologyABSTRACT
Glutamate and γaminobutyric acid (GABA) transporters serve central roles in normal neuronal activity and are associated with numerous pathological brain conditions, including ischemia and epilepsy. However, the interplay between these transporters in ischemia remains unclear. In the present study, the expression levels of the excitatory amino acid carrier 1 (EAAC1) and GABA transporter 1 (GAT1) were analyzed in vivo and in vitro within ischemic models by immunofluorescence, western blot and RTqPCR. Cell survival rates were analyzed following altered expression of these transporters within neuronal cells by flow cytometry. Expression levels of EAAC1 were reduced within the cerebrum of focal cerebral ischemic middle cerebral artery occlusion rat models as well as in primary neurons cultured under hypoxia. However, GAT1 expression levels were slightly elevated under ischemic conditions. The altered expression levels of EAAC1 and GAT1 were combined within neuron cells and the effects were investigated. Apoptotic analysis revealed that EAAC1 suppression and overexpression of GAT1 increased neuronal cell apoptosis under hypoxic conditions; however, EAAC1 overexpression combined with GAT1 knockdown reduced neuronal cell apoptosis under hypoxic conditions. The present study detected the expression levels of the glutamate and GABA transporters under hypoxia, in association with ischemia. The results indicated that, increased expression of EAAC1 combined with GAT1 suppression may provide protective effects in the treatment of epilepsy and ischemia.
Subject(s)
GABA Plasma Membrane Transport Proteins/genetics , Gene Expression , Hypoxia-Ischemia, Brain/genetics , Animals , Apoptosis/genetics , Disease Models, Animal , Excitatory Amino Acid Transporter 3/genetics , Excitatory Amino Acid Transporter 3/metabolism , GABA Plasma Membrane Transport Proteins/metabolism , Gene Knockdown Techniques , Hypoxia-Ischemia, Brain/metabolism , Male , Neurons/metabolism , RatsABSTRACT
Temozolomide (TMZ), as a kind of alkylating agent, is widely utilized for the treatment of glioblastoma (GBM). However, temozolomide resistance (TR) often develops quickly and results in tumor recurrence and poor outcome. Recent advances have demonstrated that miRNAs exert critical roles in chemoresistance. Downregulation of miR146b5p promotes glioma cell proliferation, reduces apoptosis, and correlates with poor survival of patients. Nonetheless, the function of miR146b5p in temozolomide resistance remains unclear. In the present study, we successfully generated U87 and U251TR cells, and found that miR146b5p was downregulated in TR cells. Overexpression of miR146b5p restored sensitivity of U87/U251TR cells to TMZ by targeting tumor necrosis factor receptor-associated factor 6 (TRAF6). The levels of TRAF6 were inversely related to miR146b5p levels, and overexpression of TRAF6 in miR146b5pOE cells enhanced the resistance against TMZ. Moreover, temozolomide-resistant GBM cells had a higher level of phosphorylated protein kinase B (AKT) and P65. Overexpression of miR146b5p or TRAF6 knockdown significantly decreased the level of pAKT and pp65. Collectively, our data demonstrated that miR146b5p, as a tumor suppressor, mediated temozolomide resistance in GBM cells through negatively regulating TRAF6 expression, indicating that miR146b5p and its targeted genes would be potential therapeutic targets for glioma therapy.
Subject(s)
Dacarbazine/analogs & derivatives , Glioblastoma/drug therapy , MicroRNAs/genetics , TNF Receptor-Associated Factor 6/genetics , Animals , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Dacarbazine/administration & dosage , Disease-Free Survival , Drug Resistance, Neoplasm/genetics , Female , Gene Expression Regulation, Neoplastic/drug effects , Glioblastoma/genetics , Glioblastoma/pathology , Humans , Intracellular Signaling Peptides and Proteins , Male , Mice , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Signal Transduction/drug effects , Temozolomide , Xenograft Model Antitumor AssaysABSTRACT
Forkhead transcription factor FoxO3a has been reported to have ambiguous functions and distinct mechanisms in various solid tumors, including glioblastoma (GBM). Although a preliminary analysis of a small sample of patients indicated that FoxO3a aberrations in glioma might be related to aggressive clinical behavior, the clinical significance of FoxO3a in glioblastoma remains unclear. We investigated the expression of FoxO3a in a cohort of 91 glioblastoma specimens and analyzed the correlations of protein expression with patient prognosis. Furthermore, the functional impact of FoxO3a on GBM progression and the underlying mechanisms of FoxO3a regulation were explored in a series of in vitro and in vivo assays. FoxO3a expression was elevated in glioblastoma tissues, and high nuclear FoxO3a expression in human GBM tissues was associated with poor prognosis. Moreover, knockdown of FoxO3a significantly reduced the colony formation and invasion ability of GBM cells, whereas overexpression of FoxO3a promoted the colony formation and invasion ability. The results of in vivo GBM models further confirmed that FoxO3a knockdown inhibited GBM progression. More, the pro-oncogenic effects of FoxO3a in GBM were mediated by the activation of c-Myc, microtubule-associated protein 1 light chain 3 beta (LC3B) and Beclin1 in a mixed-lineage leukemia 2 (MLL2)-dependent manner. These findings suggest that high FoxO3a expression is associated with glioblastoma progression and that FoxO3a independently indicates poor prognosis in patients. FoxO3a might be a novel prognostic biomarker or a potential therapeutic target in glioblastoma.
Subject(s)
Brain Neoplasms/genetics , Forkhead Box Protein O3/genetics , Gene Expression Regulation, Neoplastic , Glioblastoma/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Blotting, Western , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Cell Line, Tumor , Disease Progression , Female , Forkhead Box Protein O3/metabolism , Glioblastoma/metabolism , Glioblastoma/pathology , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Mice, Nude , Mice, Transgenic , Middle Aged , Neoplasm Invasiveness , Prognosis , RNA Interference , Transplantation, Heterologous , Young AdultABSTRACT
Elevated circulating asparaginyl endopeptidase (AEP), a novel lysosomal protease, has been found in breast cancer, and AEP is thus considered to be a prognostic factor in this disease. However, the pathological functions of circulating AEP in the development of breast cancer and the potential of AEP-targeted therapy remain unclear. We used MMTV-PyVmT transgenic mice, which spontaneously develop mammary tumors. Western blotting showed overexpression of AEP in both primary tumor tissue and lung metastases compared to their normal counterparts. Moreover, the concentration of circulating AEP gradually increased in the serum during the development of mammary tumors. Purified AEP protein injected through the tail vein promoted tumor growth and mammary tumor metastasis and shortened survival, whereas AEP-specific small compound inhibitors (AEPIs) effectively suppressed tumor progression and prolonged host survival. Further analysis of the molecular mechanism revealed that AEP was important for PI3K/AKT pathway activation. Thus, an elevated serum AEP level was closely related to mammary cancer progression and metastasis, and AEP is a potential target for breast cancer therapy in the clinic.
Subject(s)
Antigens, Polyomavirus Transforming/genetics , Antigens, Viral, Tumor/genetics , Cysteine Endopeptidases/genetics , Neoplasm Metastasis/genetics , Neoplasm Metastasis/pathology , Polyomavirus/genetics , Animals , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Line , Disease Progression , Female , HEK293 Cells , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Mammary Neoplasms, Experimental/genetics , Mammary Neoplasms, Experimental/pathology , Mice , Mice, Transgenic , Phosphatidylinositol 3-Kinases/genetics , Signal Transduction/geneticsABSTRACT
Neuroblastoma (NB) is one of the most commonly seen malignancies in childhood and infancy. Cantharidin is a highly potent natural toxin that possesses potent anti-tumor properties on various cancers including NB. However, exposure to cantharidin can cause severe chemical burns and application of cantharidin for cancer therapy is limited. Here we report a strategy of bundling cantharidin within a hybrid platinum (IV) prodrug conjugate. This hydrophobic drug conjugate, ie, CanPt can be further formulated into liposome for drug delivery to minimize the exposure of cantharidin to normal cells for efficient chemotherapeutic agent against NB.
Subject(s)
Cantharidin/administration & dosage , Drug Carriers/chemistry , Liposomes/chemistry , Neuroblastoma/drug therapy , Platinum/administration & dosage , Prodrugs/administration & dosage , Animals , Cell Line, Tumor , Drug Liberation , Drug Screening Assays, Antitumor , Female , Mice , Mice, Inbred BALB C , Nanoconjugates/chemistryABSTRACT
OBJECTIVE: Chronic subdural hematomas (CSDHs) are often found in neurosurgery, and display a recurrence rate of up to 37%. This study aimed to determine potential risk factors contributing to unilateral CSDH recurrence, and evaluate the role of postoperative management with dexamethasone (DX) in reducing recurrence. METHODS: Between January 2010 and May 2015, a total of 242 consecutive patients with CSDH treated with burr-hole trephination were included in this study. Univariate and multivariate analyses were performed to determine risk factors potentially associated with the recurrence of CSDH. Then, patients at high risk were divided into DX and non-DX treatment groups, respectively. Chi-square test was used to assess the potential role of DX. RESULTS: CSDH recurrence was recorded in 39 patients (16.1%). Among various risk factors, advanced age (p = .01), preoperative midline displacement exceeding 10 mm (p < .001), and hematomas presenting with separated type (p = .03) were significantly associated with CSDH recurrence. Interestingly, patients who accepted therapy with DX had a lower rate of second drainage procedure (p = .017). In addition, DX effectively reduced disease recurrence in patients with the separated type of hematoma (p = .047), and seemed to be beneficial to those with advanced age and midline shift exceeding 10 mm, although statistical significance was not achieved. CONCLUSION: These findings indicated that advanced age, midline displacement, and mixed density hematoma are independent factors for unilateral CSDH recurrence. When the above factors are detected in patients, additional DX administration should be recommended after operation.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Dexamethasone/therapeutic use , Hematoma, Subdural, Chronic/drug therapy , Hematoma, Subdural, Chronic/surgery , Trephining/methods , Adult , Age Factors , Aged , Aged, 80 and over , Combined Modality Therapy , Drainage , Female , Hematoma, Subdural, Chronic/diagnostic imaging , Humans , Male , Middle Aged , Recurrence , Retrospective Studies , Risk Factors , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
BACKGROUND: Primary intracranial germinomas occurring in the cerebral hemisphere are extremely rare, with only a few reported cases in the literature. We describe an unusual case of a primary germinoma that developed in the insular lobe, with little involvement in the basal frontal lobe. CASE DESCRIPTION: A 19-year-old man presented with headache and vomiting. Magnetic resonance imaging showed a solitary, ring-like enhanced lesion in the left hemisphere, and a preliminary diagnosis of glioma was made. Surgery was performed, and the diagnosis of germinoma was made based on the histopathologic results. CONCLUSIONS: The causes of ectopic germinomas of the midline structures of the brain are still unclear, but the theory of misplacement may partially clarify this phenomenon. Reflecting a lack of definitive management guidelines for atypical germinoma, the present patient was treated with focal radiotherapy around the lesion after surgery and achieved remission by 34 months postoperatively.
Subject(s)
Brain Neoplasms/surgery , Germinoma/surgery , Adolescent , Brain Neoplasms/radiotherapy , Cerebral Cortex , Child , Craniotomy/methods , Female , Germinoma/radiotherapy , Humans , Magnetic Resonance Imaging , Male , Young AdultABSTRACT
Exosomes, microvesicles, and other extracellular vesicles are released by many cell types, including cancer cells and cancer-related immune cells. Extracellular vesicles can directly or indirectly facilitate the transfer of bioinformation to recipient cells or to the extracellular environment. In cancer, exosomes have been implicated in tumor initiation, proliferation, and metastasis. Extracellular vesicles can transmit proteins and nucleic acids that participate in DNA methylation, histone modification, and posttranscriptional regulation of RNA. Factors transmitted by extracellular vesicles reflect the donor cell status, and extracellular vesicles derived from tumor cells may be also responsible for altering expression of tumor promoting and tumor suppressing genes in recipient cells. Thus, circulating extracellular vesicles may act as biomarkers of cancer, and detection of these biomarkers may be applied to diagnosis or assessment of prognosis in patients with cancer.