Search

Background: Nuclear factor erythroid 2-related factor 2 (NFE2L2, also known as Nrf2) is associated with cellular progression and chemotherapeutic resistance in some human cancers. We tested the relationship between Nrf2 expression and survival of patients with primary brain tumors (PBTs). Methods: In order to realize Nrf2 protein expression in gliomas, Western blot analysis was performed in normal brain tissue and U87MG, LN229, GBM8401 and U118MG glioma cell lines protein lysates. Then, U87MG, LN229, and GBM8401 mRNA were applied to performed quantitative RT-PCR for detect Nrf2 gene expression in glioma cell lines. At last, immunohistochemical analysis was used to determine the expression of Nrf2 in samples from 178 PBTs and 10 non-neoplastic brain tissues. Results: In these included in vitro studies, both Nrf2 protein and mRNA expression in all human glioma cell lines were higher than normal brain tissue. Similarly, on the viewpoint of immunohistochemistry, Nrf2 expression in gliomas were positively correlated with World Health Organization (WHO) grades. Additionally, compared with the expression of Nrf2 in non-neoplastic brain tissue, expression in meningiomas was of a stronger intensity and was present in a higher percentage of cells. Furthermore, scores were significantly higher in WHO grade II than in WHO grade I meningiomas. Finally, overall survival tended to be shorter in patients whose PBTs had higher expression of Nrf2, although the correlation was not statistically significant. Conclusions: Nrf2 overexpression positively correlated with WHO grade in gliomas and meningiomas. On the other hand, Nrf2 immunohistochemical stain could help pathologists to differentiate atypical meningiomas from benign tumors. Therefore, Nrf2 expression may be a useful biomarker to predict WHO grade and cellular behavior of PBTs. [ABSTRACT FROM AUTHOR]

Background: Nanoparticles can be used for targeted drug delivery, in particular for brain cancer therapy. However, this requires a detailed analysis of nanoparticles from the associated microvasculature to the tumor, not easy because of the required high spatial resolution. The objective of this study is to demonstrate an experimental solution of this problem, based in vivo and post-mortem whole organ imaging plus nanoscale 3-dimensional (3D) X-ray microscopy. Results: The use of gold nanoparticles (AuNPs) as contrast agents paved the way to a detailed high-resolution three dimensional (3D) X-ray and fluorescence imaging analysis of the relation between xenografted glioma cells and the tumor-induced angiogenic microvasculature. The images of the angiogenic microvessels revealed nanoparticle leakage. Complementary tests showed that after endocytotic internalization fluorescent AuNPs allow the visible-light detection of cells. Conclusions: AuNP-loading of cells could be extended from the case presented here to other imaging techniques. In our study, they enabled us to (1) identify primary glioma cells at inoculation sites in mice brains; (2) follow the subsequent development of gliomas. (3) Detect the full details of the tumor-related microvasculature; (4) Finding leakage of AuNPs from the tumor-related vasculature, in contrast to no leakage from normal vasculature. [ABSTRACT FROM AUTHOR]

Primary high-grade gliomas possess invasive growth and lead to unfavorable survival outcome. The investigation of biomarkers for prediction of survival outcome in patients with gliomas is important for clinical assessment. The DEAD (Asp-Glu-Ala-Asp) box helicase 3, X-linked (DDX3X) controls tumor migration, proliferation, and progression. However, the role of DDX3X in defining the pathological grading and survival outcome in patients with human gliomas is not yet clarified. We analyzed the DDX3X gene expression, WHO pathological grading, and overall survival from de-linked data. Further validation was done using quantitative RT-PCR of cDNA from normal brain and glioma, and immunohistochemical (IHC) staining of tissue microarray. Statistical analysis of GEO datasets showed that DDX3X mRNA expression demonstrated statistically higher in WHO grade IV (n = 81) than in non-tumor controls (n = 23, p = 1.13 × 10-10). Moreover, DDX3X level was also higher in WHO grade III (n = 19) than in non-tumor controls (p = 2.43 × 10-5). Kaplan-Meier survival analysis showed poor survival in patients with high DDX3X mRNA levels (n = 24) than in those with low DDX3X expression (n = 53) (median survival, 115 vs. 58 weeks, p = 0.0009, by log-rank test, hazard ratio: 0.3507, 95% CI: 0.1893-0.6496). Furthermore, DDX3X mRNA expression and protein production significantly increased in glioma cells compared with normal brain tissue examined by quantitative RT-PCR, and Western blot. IHC staining showed highly staining of high-grade glioma in comparison with normal brain tissue. Taken together, DDX3X expression level positively correlates with WHO pathologic grading and poor survival outcome, indicating that DDX3X is a valuable biomarker in human gliomas. [ABSTRACT FROM AUTHOR]

Background: High-grade primary gliomas are invasive and have poor outcome. The identification of biomarkers predictive of outcome in patients with gliomas is crucial for clinical follow-up. Epithelial cell transformation sequence 2 (ECT2) modulates cancer invasion, progression, metastasis and cell cycle regulation. However, its role in determining the clinical outcome of human gliomas warrants further elucidation. Materials and Methods: This study hypothesized that ECT2 is over-expressed in human gliomas. We analysis de-linked data (GDS1815/219787_s_at/ECT2) in primary high-grade glioma, and exclude 23 sheets of data without detailed information. An additional database (GDS1962/234992_x_at/ECT2) was also included to evaluation ECT2 gene expression in each pathologic grading. Results: Analysis of the Gene Expression Omnibus (GEO) profile showed that ECT2 mRNA expression level was higher in WHO grade IV (n = 81) than in grade II (n = 7, P = 0.0126) gliomas and non-tumor controls (n = 23; P = 1.65 x 10-8). Kaplan-Meier analysis showed unfavorable survival in patients with high ECT2 mRNA levels (n = 10) than in those with low ECT2 expression (n = 67) (median survival, 106 vs. 46 weeks, P < 0.0001, by log-rank test, Hazard ratio: 0.07850, 95% CI: 0.02402-0.2565). Conclusions: ECT2 expression is positively correlated with WHO pathologic grading and unfavorable survival, suggesting that ECT2 may be a potential therapeutic candidate in human gliomas. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most malignant cancer in the central nervous system with poor clinical prognosis. In this study, we investigated the therapeutic effect of an anti-cancer protein, decorin, by delivering it into a xenograft U87MG glioma tumor in the brain of nude mice through an adeno-associated viral (AAV2) gene delivery system. Decorin expression from the AAV vector in vitro inhibited cultured U87MG cell growth by induction of cell differentiation. Intracranial injection of AAV-decorin vector to the glioma-bearing nude mice in vivo significantly suppressed brain tumor growth and prolonged survival when compared to control non-treated mice bearing the same U87MG tumors. Proteomics analysis on protein expression profiles in the U87MG glioma cells after AAV-mediated decorin gene transfer revealed up- and down-regulation of important proteins. Differentially expressed proteins between control and AAV-decorin-transduced cells were identified through MALDI-TOF MS and database mining. We found that a number of important proteins that are involved in apoptosis, transcription, chemotherapy resistance, mitosis, and fatty acid metabolism have been altered as a result of decorin overexpression. These findings offer valuable insight into the mechanisms of the anti-glioblastoma effects of decorin. In addition, AAV-mediated decorin gene delivery warrants further investigation as a potential therapeutic approach for brain tumors. [ABSTRACT FROM AUTHOR]

Background: High-grade primary glioma have poor prognosis and predictive biomarkers is very important. Midkine (MDK), a heparin-binding growth factor, is important in regulating carcinogenesis, cell proliferation, mitogenesis, and angiogenesis. This study aimed to identify over-expression of MDK in gliomas and correlate this with clinical outcomes. The authors put forward their hypothesis correlating proliferation and poor survival with over-expression of this novel protein. Methods: Two datasets from Gene Expression Omnibus (GEO) included human data of 100 and 180 patients, respectively. The MDK expression, World Health Organization (WHO) pathological grade, sex, age, and survival time were identified for statistical analysis. Results: A search of the GEO profile revealed that MDK expression level was statistically greater in the WHO grade IV compared with grade II (P = 0.002), in grades III and IV compared with nontumor control (P = 0.044 and P < 0.001, respectively) after adjustments using the Bonferroni method. By the Kaplan- Meier survival curve, the high MDK expression group had poorer survival outcome (2.38-fold hazard, 95% confidence interval: 1.22-4.63) than the low MDK expression group after adjustments for WHO grade and age. Conclusions: Taken together, there is a positive correlation between MDK expression and WHO grading of human gliomas. Moreover, MDK over-expression is significant correlated to poor survival outcome in high-grade, suggesting that MDK may be an important therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Spinal manipulation is widely used for low back pain treatments. Complications associated with spinal manipulation are seen. Lumbar epidural hematoma (EDH) is one of the complications reported in the literature. If lumbar chronic EDH symptoms are present, which are similar to those of a herniated nucleus pulposus, surgery may be considered if medical treatment fails. Percutaneous endoscopic discectomy utilizing an interlaminar approach can be successfully applied to those with herniated nucleus pulposus. We use the same technique to remove the lumbar chronic EDH, which is the first documented report in the related literature. Methods: We present a case with chronic lumbar EDH associated with spinal manipulation. Neurologic deficits were noted on physical examination. We arranged for a full-endoscopic interlaminar approach to remove the hematoma for the patient with the rigid endoscopy (Vertebris system; Richard Wolf, Knittlingen, Germany). Results: After surgery, the patient's radiculopathy immediately began to disappear. Magnetic resonance imaging (MRI) follow-up 10 days after the surgery revealed no residual hematoma. No complications were noted during the outpatient department follow up. Conclusions: Lumbar EDH is a possible complication of spinal manipulation. Patient experiencing rapidly progressive neurologic deficit require early surgical evacuation, while conservative treatment may only be applied to those with mild symptoms. A percutaneous full-endoscopic interlaminar approach may be a viable alternative for the treatment of those with chronic EDH with progressive neurologic deficits. [ABSTRACT FROM AUTHOR]

Background: The transpedicular route in percutaneous vertebroplasty (PVP) is a well-established approach for the treatment of vertebral compression fractures (VCFs). However, the value of simple transpedicular biopsy in VCFs is less addressed. The purpose of this study is to evaluate the value of transpedicular biopsy during PVP for uncovering the malignancy in VCFs in a 10-year retrospective study. Materials and Methods: During the study period of the 1019 patients who underwent PVP for VCFs, 450 patients comprising of 127 male and 323 female underwent transpedicular biopsy during PVP for 705 fractured vertebras. The medical records were analyzed for age, gender, imaging studies, operation notes, pre-operative and post-operative diagnoses, date of vertebroplasty and biopsy, vertebral level and pathological reports. Results: Pathology of the specimens of the 450 patients confirmed non-malignant VCFs in 389 (86.44%) and malignancy in 61 (13.56%). The malignant pathology included: 52 (11.56%) distant metastases to vertebra, in 3 (0.67%) of the spinal metastases was unsuspected and in 49 (10.89%) of them the malignancy was suspected pre-operatively. There were 9 (2%) primary spinal malignancies, 2 (0.44%) unsuspected multiple myeloma and 7 (1.56%) pre-operatively suspected primary malignancies. The frequency of unsuspected malignancy was 1.11% (5/450) in this study. There was no complication associated with transpedicular biopsy during PVP. Conclusions: VCFs harbored 1.11% of unexpected malignancy. During the vertebroplasty, concomitant transpedicular vertebral biopsy is a safe and useful procedure for distinguishing non-malignant from malignant compression fractures, especially in diagnosing unsuspected malignancy . [ABSTRACT FROM AUTHOR]

Objective: Decompressive hemicraniectomy is accepted as the most effective life-saving treatment for malignant middle cerebral artery (MCA) infarction. However, the outcome remains hard to predict. This study examined the efficacy of using the Glasgow Coma Scale (GCS) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores before emergency craniectomy for predicting clinical outcome in malignant MCA infarction. Materials and Methods: Seventy-nine consecutive patients with malignant MCA infarction treated from January 2006 to October 2010 were retrospectively analyzed. The GCS and APACHE II scores within the first 24 h of neurological deterioration or before decompressive hemicraniectomy, were used to predict short-term functional outcome rated by the modified Rankin Scale (mRS). The receiver operating characteristic (ROC) curve was obtained to determine the accuracy and best cut-off value for each scoring system. Results: At 6 months, there was dramatic life-saving effect of surgery, with a significant reduction in mortality rate (from 71% to 19%, P <0.001). After the ROC analysis, cut-off values of pre-operative GCS >8 (P =0.003) and APACHE II <13 (P =0.006) were sufficiently sensitive and specific to predict favorable outcome (mRS 0-3). Conclusions: Pre-operative GCS and APACHE II scores are useful tools in predicting outcomes for patients with malignant MCA infarction who underwent decompressive hemicraniectomy. [ABSTRACT FROM AUTHOR]

Islet transplantation has been established as a potential therapy for type 1 diabetes. However, inflammation, allorejection, and on-going autoimmune damage contribute to early graft loss and failure of islet transplantation. Melatonin is the major secretory product of the pineal gland during the dark period of each day and displays multifunctional properties including the regulation of circadian and seasonal rhythms, antioxidation reactions and immune modulation. Based on the immunosuppressive properties of melatonin, we investigated whether melatonin treatment prolonged the survival of islet grafts in non-obese diabetic (NOD) mice. The mean islet graft survival time was 7.33 ± 1.51 and 7.75 ± 2.66 days in untreated controls and in the solvent-treated animals, respectively. Strikingly, the mean survival time of islet grafts in recipients treated with melatonin (200 mg/kg/bw) was 17 ± 7.76 days. Moreover, melatonin treatment reduced the proliferation of splenocytes in NOD mice. Using a T1 and T2 double transgenic mouse model, we found that T helper 1 (Th1) cells in mice treated with melatonin were significantly decreased. The reduction of Th1 cells and T cell proliferation may result from an increase in the immunosuppressive cytokine IL-10. Our results indicate that melatonin treatment suppresses autoimmune recurrence by inhibiting the proliferation of Th1 cells in NOD mice and thus prolongs the survival of syngeneic islet grafts. [ABSTRACT FROM AUTHOR]

Chordomas are low- to intermediate-grade malignant tumors that recapitulate the notochord. Chordomas belong to the dysontogenetic bone tumors and appear primarily in the region of the axial skeleton. Chordomas are divided into conventional, chondroid, sarcomatoid and dedifferentiated subtypes. The different subtypes of chordoma have varied survival periods. According to the literature to date, secondary pulmonary and lymph-node metastases occur most frequently, followed by liver, bone and skin metastases. To the best of our knowledge, there has been no previous report of one subtype of chordoma metastasizing or transforming into another subtype with a different histopathology. This study presents a 24-year-old man with secondary pulmonary conventional chordoma arising from a primary sarcomatoid chordoma of the sacrum. The patient was alive at the end of November, 2009 and the survival time exceeded eight years. This is the first case of a patient with primary sarcomatoid chordoma of the sacrum with complete remission in whom a secondary pulmonary conventional chordoma arose from the primary cancer. [ABSTRACT FROM AUTHOR]

Background: Closure of the dura defect may be easy to perform in open lumbar surgery but could be difficult in minimally invasive transforaminal lumbar interbody fusions (MIS-TLIF) since MIS-TLIF was done through a small tube, which limited the use of standard dural repair instruments. We used nonpenetrating titanium clips that were originally designed for the vascular anastomoses to repair the dura defect, which is never described in the literature. Methods: We presented a case of spinal stenosis with incidental durotomy while performing MIS-TLIF. We closed the dura laceration with three medium-sized nonpenetrating titanium clips (AnastoClip Vessel Closure System, LeMaitre Vascular, Inc., Burlington, MA). Results: Nonpenetrating titanium clips have the benefits of being technically easy to use, reduced durotomy repair time, decreased bed rest due to related medical complications, superior postoperation with immediate hydrostatic strength, and better reapproximation if it fails to clip successfully. As for the postoperation follow up, clips are tiny and reveal no obvious artifact, especially in cases where the pedicle screws are already causing much artifact. Conclusion: Primary dural closure during MIS-TLIF with clips is an effective way in cases that involve limited tubular space. [ABSTRACT FROM AUTHOR]

Tumors located within the third ventricle have some potential limitations during surgical approach. Generally speaking, it is impossible to reach the third ventricle without incision of any neural structure. We report a patient with choroid glioma in the anterior part of the third ventricle, and coincident cavum septum pellucidum (CSP) in whom we could remove the tumor gross totally without damaging any neurovascular structures. The tumor expanded the space between the rostrum of the corpus callosum and the column of the fornix and lifted up the floor of CSP. The transcavum-septum-pellucidum approach anterior to foramen of Monro was chosen to remove the anterior third ventricle tumor. We propose that the tumor had likely expanded within the above-mentioned space and elevated the floor of CSP thus increasing the anteroposterior diameter of the floor providing a feasible avenue to third ventricle making it feasible to pass through the enlarged space safely. Overall, cavum septum pellucidum provided a feasible route to approach the anterior third ventricle directly. [ABSTRACT FROM AUTHOR]

Abstract Introduction Using an anterior cervical fixation device in the anterior cervical discectomy and fusion (ACDF) has evolved to various systems of static and dynamic cervical plates (SCP and DCP). Dynamic cervical plates have been divided into three categories: the rotational (DCP-R), translational (DCP-T), and hybrid (DCP-H) joints. However, little studies have been devoted to systematically investigate the biomechanical differences of dynamic cervical plates. Materials and methods The biomechanical tests of load-deformation properties and failure modes between the SCP and DCP systems are implemented first by using the UHMWPE blocks as the vertebral specimens. The CT-based C2-C7 model simulates the strategies of cervical plate in ACDF surgery is developed with finite-element analyses. One intact, one SCP and two DCP systems are evaluated for their biomechanical properties of bone fusion and tissue responses. Results In the situation of biomechanical test, The mean values of the five ACDSP constructs are 393.6% for construct stiffness (p

Abstract Introduction Gliomas, a type of brain neoplasm, are prevalent and often fatal. Molecular diagnostics have improved understanding, but treatment options are limited. This study investigates the role of INTS9 in processing small nuclear RNA (snRNA), which is crucial to generating mature messenger RNA (mRNA). We aim to employ advanced bioinformatics analyses with large-scale databases and conduct functional experiments to elucidate its potential role in glioma therapeutics. Materials and methods We collected genomic, proteomic, and Whole-Exon-Sequencing data from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) for bioinformatic analyses. Then, we validated INTS9 protein expression through immunohistochemistry and assessed its correlation with P53 and KI67 protein expression. Gene Set Enrichment Analysis (GSEA) was performed to identify altered signaling pathways, and functional experiments were conducted on three cell lines treated with siINTS9. Then, we also investigate the impacts of tumor heterogeneity on INTS9 expression by integrating single-cell sequencing, 12-cell state prediction, and CIBERSORT analyses. Finally, we also observed longitudinal changes in INTS9 using the Glioma Longitudinal Analysis (GLASS) dataset. Results Our findings showed increased INTS9 levels in tumor tissue compared to non-neoplastic components, correlating with high tumor grading and proliferation index. TP53 mutation was the most notable factor associated with upregulated INTS9, along with other potential contributors, such as combined chromosome 7 gain/10 loss, TERT promoter mutation, and increased Tumor Mutational Burden (TMB). In GSEA analyses, we also linked INTS9 with enhanced cell proliferation and inflammation signaling. Downregulating INTS9 impacted cellular proliferation and cell cycle regulation during the function validation. In the context of the 12 cell states, INTS9 correlated with tumor-stem and tumor-proliferative-stem cells. CIBERSORT analyses revealed increased INTS9 associated with increased macrophage M0 and M2 but depletion of monocytes. Longitudinally, we also noticed that the INTS9 expression declined during recurrence in IDH wildtype. Conclusion This study assessed the role of INTS9 protein in glioma development and its potential as a therapeutic target. Results indicated elevated INTS9 levels were linked to increased proliferation capacity, higher tumor grading, and poorer prognosis, potentially resulting from TP53 mutations. This research highlights the potential of INTS9 as a promising target for glioma treatment.

Abstract Glioblastoma is the most common primary central nervous system tumor in adults. Angiotensin II receptor blockers (ARBs) are broadly applied to treat hypertension. Moreover, research has revealed that ARBs have the capacity to suppress the growth of several cancer types. In this study, we assessed the effects of three ARBs with the ability to cross the blood brain barrier (telmisartan, valsartan and fimasartan) on cell proliferation in three glioblastoma multiforme (GBM) cell lines. Telmisartan markedly suppressed the proliferation, migration, and invasion of these three GBM cell lines. Microarray data analysis revealed that telmisartan regulates DNA replication, mismatch repair, and the cell cycle pathway in GBM cells. Furthermore, telmisartan induced G0/G1 phase arrest and apoptosis. The bioinformatic analysis and western blotting results provide evidence that SOX9 is a downstream target of telmisartan. Telmisartan also suppressed tumor growth in vivo in an orthotopic transplant mouse model. Therefore, telmisartan is a potential treatment for human GBM.