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Among the most biologically, thus clinically, aggressive primary brain tumors are found malignant gliomas. Despite recent advances in adjuvant therapies, which include targeted and immunotherapies, after surgery and radio/chemotherapy, the tumor is recurrent and always lethal. Malignant gliomas also contain a pool of initiating stem cells that are highly invasive and resistant to conventional treatment. Ion channels and transporters are markedly involved in cancer cell biology, including glioma cell biology. Transient receptor potential (TRP) ion channels are calcium-permeable channels implicated in Ca2+ changes in multiple cellular compartments by modulating the driving force for Ca2+ entry. Recent scientific reports have shown that these channels contribute to the increase in glioblastoma aggressiveness, with glioblastoma representing the ultimate level of glioma malignancy. The current review focuses on each type of TRP ion channel potentially involved in malignant glioma cell death, with the ultimate goal of identifying new therapeutic targets to clinically combat malignant gliomas. It thus appears that cannabidiol targeting the TRPV2 type could be such a potential target.

Objective: Implantation of biodegradable Carmustine wafers in patients with malignant glioma is not generally recommended when the ventricular system is opened during tumor resection. Thrombin/fibrinogenn-covered collagen fleeces showed promising results in sufficiently closing ventricular defects. The aim of this study was to evaluate the postoperative morbidity in patients with implanted Carmustine wafers either with opened or intact ventricular system. Methods: A consecutive series of patients who underwent resection of malignant glioma with implantation of Carmustine wafers was analyzed. In case of opening of the ventricular system, the defect in the ventricle wall was sealed using a collagen sponge coated with fibrinogen and thrombin prior to the implantation of the wafers. Postoperative adverse events (AE) and Karnofsky performance status scale (KPS) at follow up were compared between both groups. Results: Fifty-four patients were included. The ventricular system was opened in 33 patients and remained intact in 21 patients. Both groups were comparable in terms of age, rate of primary and recurrent glioma, preoperative KPS, rate of gross total resection and number of implanted wafers. Postoperative AEs occurred in 9/33 patients (27.3%) with opened and in 5/21 patients (23.8%) with intact ventricular system (p = 0.13). At follow-up assessments, KPS was not significantly different between both groups (p = 0.18). Opened ventricular system was not associated with a higher incidence of postoperative AEs (p = 0.98). Conclusion: Appropriate closure of opened ventricular system during resection of malignant glioma allows for a safe implantation of Carmustine wafers and is not associated with a higher incidence of postoperative AEs. [ABSTRACT FROM AUTHOR]

Background End-of-life discussions (EOLDs) in patients with high-grade glioma (HGG) have not been well described. Therefore, this study examined the appropriateness of timing and the extent of patient involvement in EOLDs and their impact on HGG patients. Methods A cross-sectional survey was conducted among 105 bereaved families of HGG patients at a university hospital in Japan between July and August 2019. Fisher's exact test and the Wilcoxon rank-sum test were used to assess the association between patient participation in EOLDs and their outcomes. Results In total, 77 questionnaires were returned (response rate 73%), of which 20 respondents replied with refusal documents. Overall, 31/57 (54%) participated in EOLDs at least once in acute hospital settings, and a significant difference was observed between participating and nonparticipating groups in communicating the patient's wishes for EOL care to the family (48% vs 8%, P =.001). Moreover, >80% of respondents indicated that the initiation of EOLDs during the early diagnosis period with patients and families was appropriate. Most EOLDs were provided by neurosurgeons (96%), and other health care providers rarely participated. Additionally, patient goals and priorities were discussed in only 28% of the EOLDs. Patient participation in EOLDs was not associated with the quality of EOL care and a good death. Conclusions Although participation in EOLDs is relatively challenging for HGG patients, this study showed that participation in EOLDs may enable patients to express their wishes regarding EOL care. It is important to initiate EOLDs early on through an interdisciplinary team approach while respecting patient goals and priorities. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of chromosome 10 deletion phosphatase and tensin homolog( PTEN) expression on radiosensitivity of malignant glioma cells and its mechanism. Methods Real time quantitative polymerase chain reaction(RT-qPCR) and Western blot were used to detect the expression of PTEN mRNA and protein in malignant glioma and adjacent normal tissues and cells. The expression of PTEN was detected by RT-qPCR and Western blot. Results Compared with the normal tissues, PTEN mRNA and protein expression in malignant glioma were significantly decreased(P<0.01). The expression of PTEN mRNA and protein in U251 cells and T98G cells of malignant glioma was significantly lower than that of normal brain gliocytes (P<0.05-0. 01). The PTEN expression of T98G cells increased with the increase of X-ray dose. Conclusion Down regulation of PTEN gene expression can activate Pl3K-AKT-GSK3β signal pathway, thereby reducing the radiosensitivity of malignant glioma cell. [ABSTRACT FROM AUTHOR]

Malignant glioma is a highly fatal type of brain tumor, and its reoccurrence is largely due to the ordered interactions among the components present in the complex microenvironment. Besides its role in immune surveillance and clearance under physiological conditions, the complement system is expressed in a variety of tumor types and mediates the interactions within the tumor microenvironments. Recent studies have uncovered the broad expression spectrum of complement signaling molecules in the tumor microenvironment and various tumor cells, in particular, malignant glioma cells. Involvement of the complement system in tumor growth, immunosuppression and phenotype transition have also been elucidated. In this review, we enumerate the expression and function of complement molecules in multiple tumor types reported. Moreover, we elaborate the complement pathways in glioma cells and various components of malignant glioma microenvironments. Finally, we summarize the possibility of the complement molecules as prognostic factors and therapeutic targets in the treatment of malignant glioma. Specific targeting of the complement system maybe of great significance and value in the future treatment of multi-type tumors including malignant glioma.

Glioblastoma Multiforme (GMB) is the most aggressive primary brain tumor with poor survival rates and universal recurrence despite aggressive treatments. Recent research suggested that GBM has multiple glioma cell populations, some of which are organized in a stem cell hierarchical order with different stages of differention. Evidence indicated that recurrence is due to a development or persistance of a subpopulation of these tumor cells which are inherently resistant to treatment and these were defined as the glioma stem-like cells (GSC). It is hypothesized that GSC become highly malignant by accumulating mutations in oncogenic pathways. These cells present with specific surface markers which helps identify them. Targeting the surface markers as well as the signaling pathways of GSCs has been an ongoing research effort. This review focuses on summarizing the current treatment modalities used to glioblastoma treatments, evaluating their efficacy in controlling and eradicatig the GSCs, discussing the machanisms involved in GSC tumor proliferation and resistance to treatments in addition to proposing potential avenues to target GSCs in order to provide a potential cure for this cancer.

TRIM11 (tripartite motif-containing protein 11), an E3 ubiquitin ligase, is known to be involved in the development of the central nervous system. However, very little is known regarding the role of TRIM11 in cancer biology. Here, we examined the expression profile of TRIM11, along with two stem cell markers CD133 and nestin, in multiple glioma patient specimens, glioma primary cultures derived from tumors taken at surgery and normal neural stem/progenitor cells (NSCs). The oncogenic function of TRIM11 in glioma biology was investigated by knockdown and/or overexpression in vitro and in vivo experiments. Our results showed that TRIM11 expression levels were upregulated in malignant glioma specimens and in high-grade glioma-derived primary cultures, whereas remaining low in glioblastoma multiforme (GBM) stable cell lines, low-grade glioma-derived primary cultures and NSCs. The expression pattern of TRIM11 strongly correlated with that of CD133 and nestin and differentiation status of malignant glioma cells. Knock down of TRIM11 inhibited proliferation, migration and invasion of GBM cells, significantly decreased epidermal growth factor receptor (EGFR) levels and mitogen-activated protein kinase activity, and downregulated HB-EGF (heparin-binding EGF-like growth factor) mRNA levels. Meanwhile, TRIM11 overexpression promoted a stem-like phenotype in vitro (tumorsphere formation) and enhanced glial tumor growth in immunocompromised mice. These findings suggest that TRIM11 might be an indicator of glioma malignancy and has an oncogenic function mediated through the EGFR signaling pathway. TRIM11 overexpression potentially leads to a more aggressive glioma phenotype, along with increased malignant tumor growth and poor survival. Taken together, clarification of the biological function of TRIM11 and pathways it affects may provide novel therapeutic strategies for treating malignant glioma patients.

Systemically infused mesenchymal stem cells (MSCs) are emerging therapeutics for treating stroke, acute injuries, and inflammatory diseases of the central nervous system (CNS), as well as brain tumors due to their regenerative capacity and ability to secrete trophic, immune modulatory, or other engineered therapeutic factors. It is hypothesized that transplanted MSCs home to and engraft at ischemic and injured sites in the brain in order to exert their therapeutic effects. However, whether MSCs possess the ability to migrate across the blood-brain barrier (BBB) that separates the blood from the brain remains unresolved. This review analyzes recent advances in this area in an attempt to elucidate whether systemically infused MSCs are able to actively transmigrate across the CNS endothelium, particularly under conditions of injury or stroke. Understanding the fate of transplanted MSCs and their CNS trafficking mechanisms will facilitate the development of more effective stem-cell-based therapeutics and drug delivery systems to treat neurological diseases and brain tumors.

AMPA receptors are tetrameric glutamate‐gated ion channels that mediate a majority of fast excitatory neurotransmission in the brain. They exist as calcium‐impermeable (CI‐) and calcium‐permeable (CP‐) subtypes, the latter of which lacks the GluA2 subunit. CP‐AMPARs display an array of distinctive biophysical and pharmacological properties that allow them to be functionally identified. This has revealed that they play crucial roles in diverse forms of central synaptic plasticity. Here we summarise the functional hallmarks of CP‐AMPARs and describe how these are modified by the presence of auxiliary subunits that have emerged as pivotal regulators of AMPARs. A lasting change in the prevalence of GluA2‐containing AMPARs, and hence in the fraction of CP‐AMPARs, is a feature in many maladaptive forms of synaptic plasticity and neurological disorders. These include modifications of glutamatergic transmission induced by inflammatory pain, fear conditioning, cocaine exposure, and anoxia‐induced damage in neurons and glia. Furthermore, defective RNA editing of GluA2 can cause altered expression of CP‐AMPARs and is implicated in motor neuron damage (amyotrophic lateral sclerosis) and the proliferation of cells in malignant gliomas. A number of the players involved in CP‐AMPAR regulation have been identified, providing useful insight into interventions that may prevent the aberrant CP‐AMPAR expression. Furthermore, recent molecular and pharmacological developments, particularly the discovery of TARP subtype‐selective drugs, offer the exciting potential to modify some of the harmful effects of increased CP‐AMPAR prevalence in a brain region‐specific manner. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the efficacy of Gamma Knife radiosurgery (GKRS) as a salvage therapy for high-grade glioma in our center. Methods: A total of 167 patients with malignant glioma were treated with GKRS in our Gamma Knife Center between January 2013 and December 2017; 140 patients (85 males and 55 females) were followed up and enrolled in our study. A single lesion was found in 110 cases, and multiple lesions were found in 30 cases; 108 cases received a single therapy, and in 32 cases, at least 2 GKRSs were performed. The median tumor volume was 13.5 cm3. The mean radiation dosage was 14.35 Gy (range, 6–18 Gy). MRI was performed regularly. The RANO criteria and Cox analysis were used to evaluate the therapeutic efficiency. Results: Follow-up MRI showed the local control rate was 61.4% at 3 months after GKRS, 25.0% at 6 months, and 7.1% at 12 months. The mean and median progression-free survival (PFS) periods were 8.6 (95% CI, 6.3–11.0) and 4 (95% CI, 3.5–4.5) (range, 1–60) months, respectively. The overall survival (OS) after GKRS was 3–62 months, with a mean of 16.7 (95% CI, 14.6–18.9) months, and the median survival was 13 (95% CI, 12.1–13.9) months. The 1-, 2-, and 5-year survival rates were 51.4, 10.0, and 2.9%, respectively. No severe complications occurred. Cox regression showed that glioma pathology was closely related to prognosis (p < 0.05). The Karnofsky Performance Score had little influence on PFS (p > 0.05) but influenced OS significantly (p < 0.05). Conclusion: GKRS can be used to effectively treat malignant brain glioma and can therefore be used as an alternative treatment option. [ABSTRACT FROM AUTHOR]

A prospective cohort study was structured to examine patient's tumor mass factors that could determine a specific cognitive function profile in patients with Malignant Glioma who survived after the Stupp protocol, while adjusting for previously explored confounding factors. Neuropsi - Attention and Memory (Second edition) was applied after tumor resection, but before any other oncological treatment. Follow-up neuropsychological evaluation was conducted when patients completed the Stupp protocol treatment scheme. To estimate the mean difference between follow-up and baseline Neuropsi subtest scores, a Bayesian Mixed Effects Model was fitted with three random-effect regressors representing tumor locations, co-administered medications and by-patient cognitive performance variability. Sixteen patients were included. Temporal lobe tumors were the most frequent (31.2%) and more than three-fourths of those were located in the left lobe; such results agree with the clinical and statistical significance that supports an impairment in the Semantic Verbal Fluency subtest (Mean score change = -5.97, 95% Credible Interval = [-8.01, -3.80]). The findings suggest that any potential variants in a determined cognitive dysfunction profile could be more influenced by tumor location than any other variable related to the patient's tumor mass or administered oncological medications; however, because the limited sample representativeness, additional studies are required. [ABSTRACT FROM AUTHOR]

Background: Family and friend caregivers play a critical role in advance care planning (ACP) discussions, which are difficult but necessary to carry out patients' goals of care. This role is particularly important among caregivers of patients with malignant gliomas (MGs), who are often tasked with quickly taking responsibility for healthcare communication. We developed and evaluated the feasibility, acceptability, and preliminary effects of a virtual communication training program to equip caregivers of patients with recurrent MGs with skills to navigate ACP conversations with patients and healthcare providers., Methods: Our two-hour communication skills training combined a series of didactic exercises with role-play scenarios, as well as follow-up coaching via a booster call conducted two-weeks after training completion. Caregivers were randomized to receive either the Communication Skills Training or Enhanced Usual Care (EUC), which included screening and the provision of targeted referrals. Assessments were completed at baseline (T1) and at two- (T2) and five-months (T3) follow-up., Results: Thirty-four caregivers enrolled and were randomized, of whom 19 completed the T2 and 18 completed the T3 assessment. Ten of the 13 caregivers who completed the training participated in interviews at T2 about their experiences and perceived benefits of participation. At T3, results indicated a strong effect size for reduced anxiety and distress, and increased preparedness for death in caregivers who received the intervention relative to EUC. Participants reported the training helped them feel confident initiating ACP conversations, validated in their fears about death, and helped them feel supported and less alone., Conclusion: Despite the challenges of recruiting a highly distressed group of caregivers, there were notable benefits of our Communication Skills Training. Additional larger trials are needed to rigorously evaluate the efficacy of the training program and those that include caregivers of patients with other sites and stages of cancer to determine the generalizability of findings.

Chronic encapsulated intracerebral hematoma is a rare type of intracerebral hemorrhage. Reportedly, it is associated with vascular malformations, including arteriovenous malformations, cavernous hemangiomas, microaneurysms, and venous malformations. Recently, an association between chronic encapsulated intracerebral hematoma and stereotactic radiosurgery for arteriovenous malformations has been reported. In general, as the hematoma enlarges, symptoms progress slowly. In this report, we present a case of a 50-year-old woman who had undergone clivus chordoma resection and carbon ion therapy for the clivus respectively 27 and 20 years before developing chronic encapsulated intracerebral hematoma with rapidly progressing disturbance of consciousness. She was referred to our hospital because of difficulty walking due to left hemiparesis. Head computed tomography and magnetic resonance imaging showed a cystic lesion in the right temporal lobe with perifocal edema. On the second day of hospitalization, the patient's consciousness worsened. We suspected a malignant glioma and performed an emergency craniotomy; however, the pathological diagnosis was chronic encapsulated intracerebral hematoma. After the rehabilitation therapy, the patient became ambulatory and was discharged. To the date of reporting, the patient remained recurrence-free. Chronic encapsulated intracerebral hematoma may be due to invasive craniotomy or carbon ion therapy. It usually progresses slowly; however, in some cases, such as this one, it may cause rapid deterioration of consciousness., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Japan Neurosurgical Society.)

The activity of single-agent targeted molecular therapies in glioblastoma has been limited to date. The North American Brain Tumor Consortium examined the safety, pharmacokinetics, and efficacy of combination therapy with sorafenib, a small molecule inhibitor of Raf, vascular endothelial growth factor receptor 2, and platelet-derived growth factor receptor-β, and temsirolimus (CCI-779), an inhibitor of mammalian target of rapamycin. This was a phase I/II study. The phase I component used a standard 3 × 3 dose escalation scheme to determine the safety and tolerability of this combination therapy. The phase II component used a 2-stage design; the primary endpoint was 6-month progression-free survival (PFS6) rate. Thirteen patients enrolled in the phase I component. The maximum tolerated dosage (MTD) for combination therapy was sorafenib 800 mg daily and temsirolimus 25 mg once weekly. At the MTD, grade 3 thrombocytopenia was the dose-limiting toxicity. Eighteen patients were treated in the phase II component. At interim analysis, the study was terminated and did not proceed to the second stage. No patients remained progression free at 6 months. Median PFS was 8 weeks. The toxicity of this combination therapy resulted in a maximum tolerated dose of temsirolimus that was only one-tenth of the single-agent dose. Minimal activity in recurrent glioblastoma multiforme was seen at the MTD of the 2 combined agents.

UnlabelledWith the dismal prognosis for malignant glioma patients, survival predictions become key elements in patient management. This study compares the value of 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) PET and MRI for early outcome predictions in patients with recurrent malignant glioma on bevacizumab therapy.MethodsThirty patients treated with bevacizumab combination therapy underwent (18)F-FLT PET immediately before and at 2 and 6 wk after the start of treatment. A metabolic treatment response was defined as a decrease of equal to or greater than 25% in tumor (18)F-FLT uptake (standardized uptake values) from baseline using receiver-operating-characteristic analysis. MRI treatment response was assessed at 6 wk according to the Response Assessment in Neurooncology criteria. (18)F-FLT responses at different times were compared with MRI response and correlated with progression-free survival and overall survival using Kaplan-Meier analysis. Metabolic response based on (18)F-FLT was further compared with other outcome predictors using Cox regression analysis.ResultsEarly and late changes in tumor (18)F-FLT uptake were more predictive of overall survival than MRI criteria (P < 0.001 and P = 0.01, respectively). (18)F-FLT uptake changes were also predictive of progression-free survival (P < 0.001). The median overall survival for responders was 3.3 times longer than for nonresponders based on (18)F-FLT PET criteria (12.5 vs. 3.8 mo, P < 0.001) but only 1.4 times longer using MRI assessment (12.9 vs. 9.0 mo, P = 0.05). On the basis of the 6-wk (18)F-FLT PET response, there were 16 responders (53%) and 14 nonresponders (47%), whereas MRI identified 9 responders (7 partial response, 2 complete response, 31%) and 20 nonresponders (13 stable disease, 7 progressive disease, 69%). In 7 of the 8 discrepant cases between MRI and PET, (18)F-FLT PET was able to demonstrate response earlier than MRI. Among various outcome predictors, multivariate analysis identified (18)F-FLT PET changes at 6 wk as the strongest independent survival predictor (P < 0.001; hazard ratio, 10.051).ConclusionChanges in tumor (18)F-FLT uptake were highly predictive of progression-free and overall survival in patients with recurrent malignant glioma on bevacizumab therapy. (18)F-FLT PET seems to be more predictive than MRI for early treatment response.

GBM (glioblastoma multiforme) is the most common and aggressive brain tumor. To date, treatment options for glioblastoma recurrence are lacking. Recently, REGOMA trial showed the superiority of regorafenib to lomustine in patients with first glioblastoma recurrence. We report an excellent response to three months treatment with regorafenib, in a patient who presented a rapid progression after the end of post operative radio-chemotherapy and after only one cycle of adjuvant TMZ (Temozolomide).

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Malignant gliomas are rapidly growing tumours that extensively invade the brain and have bad prognosis. Our study was performed to assess the metabolic effects of bevacizumab on the glioma cells carrying the IDH1 mutation, a mutation, associated with better prognosis and treatment outcome. Bevacizumab is known to inhibit tumour growth by neutralizing the biological activity of vascular endothelial growth factor (VEGF). However, the direct effects of bevacizumab on tumour cells metabolism remain poorly known.

Abstract Background This study aimed to analyze the relationship between molecular pathologic expression of GFAP and Ki-67 and fluorescence levels, and to provide molecular pathological basis for the removal of malignant gliomas (MG) by Fluorescein Sodium (FLS) navigation under the YELLOW 560 nm surgical microscope filter. Methods A retrospective analysis of clinical data of 18 MG cases confirmed by the postoperative pathology was performed. All cases were resected by FLS guiding under the YELLOW 560 nm filter. Hematoxylin-eosin (HE) staining, molecular pathology markers GFAP, and Ki-67 immunohistochemical staining of the specimens were performed. The relationship between fluorescence staining levels and GFAP positive rate, Ki-67 proliferation index, and WHO grades was studied. Results There were 69 pathological specimens with fluorescence levels of “bright” fluorescence (n = 32), “low” fluorescence (n = 18), and “no” fluorescence (n = 19). Immunohistochemical staining showed GFAP-positive expression in both tumor cells and normal glial cells. The staining levels of the specimens in the fluorescence regions were higher than that in the non-fluorescence regions. GFAP expression was positive in 61 specimens and negative in 8 specimens. Comparison of Ki-67 proliferation index using chi-square test showed different fluorescence levels had different Ki-67 proliferation indexes (χ 2 = 14.678, p = 0.005). With high proliferation index of specimens, fluorescence level was brighter. WHO grade had no correlation with fluorescence levels (χ 2 = 3.531, p = 0.171). Conclusion FLS-guided resection of MG is safe and effective. In the boundary area of MG, fluorescence levels and Ki-67 proliferation index showed correlation. FLS-guided resection achieved the function of “reducing tumor cell,” thus reducing the proliferation index in the lesion area.

Introduction: The purpose of this study is to clarify the clinical features of temozolomide (TMZ)-related hepatitis B virus (HBV) reactivation and to identify HBV reactivation predictive factors. Method: We retrospectively reviewed the clinical course of 145 patients newly diagnosed or with recurrent malignant glioma treated with TMZ. Before treatment, we screened patients for HB surface antigen (HBsAg) positivity (HBV carrier) and HBsAg negativity. Patients were also screened for antibody for HB core antigen (anti-HBc) positivity and/or for HB surface antigen positivity (resolved HBV infection). The patients were monitored by HBV DNA, alanine, and aspartate aminotransaminase during and after the completion of TMZ. HBV carriers and those with resolved HBV infections with HBV reactivation received preemptive entecavir treatment. In those with resolved HBV infections, we analyzed clinical characters for the predictive factors for HBV reactivation. Results: In one of two HBV carriers, HBV DNA turned positive 8 months after the completion of TMZ and entecavir. In four (16.7%) of 24 resolved HBV infections, HBV DNA turned detectable at completion of concomitant radiation and TMZ or during monthly TMZ. HBV DNA turned negative with entecavir in all patients without liver dysfunction. In resolved HBV infections, those with a high anti-HBc titer had significantly higher incidence of HBV reactivation than those with low anti-HBc titers (60% vs. 5.3%: p = 0.018). Conclusion: Screenings, monitoring, and preemptive entecavir were important for preventing TMZ-related HBV reactivations. Anti-HBc titers could be the predictive markers for HBV reactivation in the those with resolved HBV infections. [ABSTRACT FROM AUTHOR]

Malignant gliomas are still extremely difficult to treat because complete surgical resection is biologically not feasible due to the invasive nature of these diseases and the proximity of tumors to functionally sensitive areas. Moreover, adjuvant therapies are facing a strong therapeutic resistance since the central nervous system is a highly protected environment and the tumor cells display a vast intra-tumoral genetic and epigenetic variation. As a consequence, new therapeutics are urgently needed but the process of developing novel compounds that finally reach clinical application is highly time-consuming and expensive. Drug repurposing is an approach to facilitate and accelerate the discovery of new cancer treatments. In malignant glioma, like in other cancers, pre-existing physiological pathways that regulate cell growth, cell death or cell migration are dysregulated causing malignant transformation. A wide variety of drugs are clinically used to treat non-cancerous diseases interfering with these malignancy-associated pathways. Repurposed drugs have key advantages: They already have approval for clinical use by national regulatory authorities. Moreover, they are for the most part inexpensive and their side effect and safety profiles are well characterized. In this work, we provide an overview on current repurposing strategies for the treatment of malignant glioma. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of exosomes divided from human bone marrow mesenchymal stem cells on the polarization of tumor-associated macrophages, and to preliminarily discuss their influence on glioma cell lines. Methods Exosomes divided from human bone marrow mesenchymal stem cells were extracted and identified by scanning electron microscopy and western blot. The glioma cell line SHG449 was divided into three groups: SHG449 group: SHG449 cells without special treatment; SHG449+M0 group：SHG449 cells co-cultured with M0 macrophages; SHG449+M0+exosome group: SHG449 cells co-cultured with M0 macrophages, and then exosomes labeled with PKH-67 were added to the M0 cells. The mRNA expression of M1 biomarkers (iNOS and CD68） and M2 markers（ Arginase and CD206） were detected by qPCR, and the content of IL-1β, TNF-α, CCL22 and TGF-β in the supernatant of SHG449 cells were detected by ELISA. The proliferation and apoptosis of SHG449 cell line were detected by CCk8 and flow cytometry. Results (1）Exosomes secreted by human bone marrow mesenchymal stem cells were successfully extracted and entered into M0-type macrophages.（2）Macrophage morphology was transformed after exosome was intaken by SHG449-induced polarized macrophages， and the expression of M2 macrophages markers Arginase，CD206，CCL22 and TGF-β were decreased（Arginase：P < 0.01, CD206：P < 0.05， CCL22：P < 0.05，TGF-β：P < 0.01)，while the expression of M1 macrophages markers iNOS，CD68，IL-1β and TNF-α increased（iNOS：P < 0.01，CD68：P < 0.01，L-1β：P < 0.000 1， TNF-α: P < 0.001).（3）Macrophage polarization induced by exosomes resulted in decreased proliferation（P < 0.05） and increased apoptotic（P < 0.000 1） of glioma cells. Conclusion Exosomes derived from human bone marrow stromal cells can inhibit the polarization of tumor-associated macrophages to the M2 phenotype and induce their polarization to the M1 phenotype, and regulate the tumor immune microenvironment, thereby suppressing the development of glioma. [ABSTRACT FROM AUTHOR]

Introduction : Laser interstitial thermal therapy (LITT) remains a promising advance in the treatment of primary central nervous system malignancies. As indications for its use continue to expand, there has been growing interest in its ability to induce prolonged blood brain barrier (BBB) permeability through hyperthermia, potentially increasing the effectiveness of current therapeutics including BBB-impermeant agents and immunotherapy platforms. Methods: In this review, we highlight the mechanism of hyperthermic BBB disruption and LITT-induced immunogenic cell death in preclinical models and humans. Additionally, we summarize ongoing clinical trials evaluating a combination approach of LITT and immunotherapy, which will likely serve as the basis for future neuro-oncologic treatment paradigms. Results: There is evidence to suggest a highly immunogenic response to laser interstitial thermal therapy through activation of both the innate and adaptive immune response. These mechanisms have been shown to potentiate standard methods of oncologic care. There are only a limited number of clinical trials are ongoing to evaluate the utility of LITT in combination with immunotherapy. Conclusion: LITT continues to be studied as a possible technique to bridge the gap between exciting preclinical results and the limited successes seen in the field of neuro-oncology. Preliminary data suggests a substantial benefit for use of LITT as a combination therapy in several clinical trials. Further investigation is required to determine whether or not this treatment paradigm can translate into long-term durable results for primary intracranial malignancies. [ABSTRACT FROM AUTHOR]

Background: 5-Aminolevulinic Acid (5-ALA) photodiagnosis (PD) is an effective method to detect residual tumors during glioma surgery. However, fluorescence strength differs in malignant gliomas, and false-negative fluorescence may result in tumor residue. We investigated the effect of ultrasound on the intracellular level of protoporphyrin IX (PpIX) and expression level of ATP-binding cassette transporter 2 (ABCG2), which is thought to act as a membrane efflux pump of PpIX from cytosol. Methods: The malignant glioma cell lines SNB19, U87MG, and T98G were used for in vitro experiments. Cultured cells underwent ultrasound irradiation (1 MHz, 3 W/cm2, duty cycle 10%) after administration of 5-ALA, and morphological changes in tumor cells were observed. PpIX levels and ABCG2 expression were evaluated. Results: The glioma tumor cells showed transient morphological changes and detachment from the culture dish; however, most cells survived and reverted to their original morphology within 6 hours. PpIX expression levels increased in glioma cells after ultrasound irradiation, and the increase was earlier and greater than that for 5-ALA alone. ABCG2 expressions increased after 5-ALA administration but were lower in ultrasound-irradiated glioma cells. Conclusions: Ultrasound irradiation of malignant gliomas contributes to stronger 5-ALA-induced fluorescence by elevating intracellular PpIX levels. Suppression of ABCG2 expression by ultrasound may contribute to PpIX accumulation in glioma cells. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluates the application of a microdialysis technique for interstitial chemotherapy using cisplatin in high-grade glioma. Method: An in vitro study demonstrated that cisplatin can be administered through retrograde microdialysis and defined the recovery for cisplatin. In a subsequent phase I study, 1–4 microdialysis catheters were implanted in tumor tissue, brain adjacent to tumor (BAT) tissue, and subcutaneous tissue in 10 patients with recurrent high-grade glioma. Cisplatin was administered continuously in daily doses between 0.3 and 3.9 mg for 4 to12 days. Microdialysis samples were continuously collected and analyzed for glucose metabolites, glutamate, glycerol, and cisplatin concentrations. Treatment tolerability was evaluated through clinical monitoring. Quality of life was assessed using the EORTC-QLQ-C30 questionnaire for up to 3 months after treatment. Results: This in vitro study showed that cisplatin could be administrated with a recovery of 41–97%, depending on flowrate, type of catheter, and cisplatin concentration. During the treatment, patients were exposed to a total dose of 1.2–36.8 mg cisplatin. The concentration of cisplatin in BAT, serum, and subcutaneous tissue was close to detection level in all but two patients. A transient neurologic deterioration due to edema was commonly observed, but no systemic side effects were recorded. After onset of treatment, concentrations of glutamate and glycerol were significantly increased in tumor tissue but not in BAT, with a peak after 3 days, and consistent for the rest of the treatment. Five of the patients survived between 153 and 492 days after treatment. Conclusion: This phase I study demonstrates that retrograde microdialysis can be used to administer cisplatin interstitially into high-grade glioma tissue. A high cytotoxicity was detected in tumor tissue, but not in the surrounding brain. Retrograde microdialysis appears to be a clinically useful method for intratumoral drug administration in high-grade glioma. [ABSTRACT FROM AUTHOR]

The molecular biology of human glioma is a complex and fast-growing field in which basic research needs to meet clinical expectations in terms of anti-tumor efficacy. Although much effort is being done in molecular biology research, significant contribution to the quality of life and overall survival still lacks. The vastness of molecular biology literature makes it virtually impossible for clinicians to keep up to date in the field. This paper reviews some practical concepts regarding glioma tumorigenesis from the clinician's perspective. Five main aspects are discussed: major intracellular signaling pathways involved in glioma formation; genomic, epigenetic and transcriptomic relevant features of glioma; the prognostic and predictive values of molecular markers according to the new WHO classification of glial tumors; the importance of molecular and cellular heterogeneity in glioblastoma, responsible for its therapy resistance; and the interaction between glioma and the immune system, in view of the novel and promising targeted therapies. [ABSTRACT FROM AUTHOR]

Background Patients with malignant gliomas have a poor prognosis. However, little is known about patients' and caregivers' understanding of the prognosis and the primary treatment goal. Methods We conducted a prospective study in patients with newly diagnosed malignant gliomas (N = 72) and their caregivers (N = 55). At 12 weeks after diagnosis, we administered the Prognosis and Treatment Perceptions Questionnaire to assess understanding of prognosis and the Hospital Anxiety and Depression Scale to evaluate mood. We used multivariable regression analyses to explore associations between prognostic understanding and mood and McNemar tests to compare prognostic perceptions among patient-caregiver dyads (N = 48). Results A total of 87.1% (61/70) of patients and 79.6% (43/54) of caregivers reported that it was "very" or "extremely" important to know about the patient's prognosis. The majority of patients (72.7%, [48/66]) reported that their cancer was curable. Patients who reported that their illness was incurable had greater depressive symptoms (B = 3.01, 95% CI, 0.89-5.14, P =.01). There was no association between caregivers' prognostic understanding and mood. Among patient-caregiver dyads, patients were more likely than caregivers to report that their primary treatment goal was cure (43.8% [21/48] vs 25.0% [12/48], P =.04) and that the oncologist's primary goal was cure (29.2% [14/48] vs 8.3% [4/48], P =.02). Conclusions Patients with malignant gliomas frequently hold inaccurate perceptions of the prognosis and treatment goal. Although caregivers more often report an accurate assessment of these metrics, many still report an overly optimistic perception of prognosis. Interventions are needed to enhance prognostic communication and to help patients cope with the associated distress. [ABSTRACT FROM AUTHOR]

Background: Pseudoprogression (PP) and treatment‐induced brain tissue necrosis (TN) are challenging cancer treatment–related effects. Both phenomena remain insufficiently defined; differentiation from recurrent disease frequently necessitates tissue biopsy. We here characterize distinctive features of PP and TN to facilitate noninvasive diagnosis and clinical management. Materials and Methods: Patients with glioma and confirmed PP (defined as appearance <5 months after radiotherapy [RT] completion) or TN (>5 months after RT) were retrospectively compared using clinical, radiographic, and histopathological data. Each imaging event/lesion (region of interest [ROI]) diagnosed as PP or TN was longitudinally evaluated by serial imaging. Results: We identified 64 cases of mostly (80%) biopsy‐confirmed PP (n = 27) and TN (n = 37), comprising 137 ROIs in total. Median time of onset for PP and TN was 1 and 11 months after RT, respectively. Clinically, PP occurred more frequently during active antineoplastic treatment, necessitated more steroid‐based interventions, and was associated with glioblastoma (81 vs. 40%), fewer IDH1 mutations, and shorter median overall survival. Radiographically, TN lesions often initially manifested periventricularly (n = 22/37; 60%), were more numerous (median, 2 vs. 1 ROIs), and contained fewer malignant elements upon biopsy. By contrast, PP predominantly developed around the tumor resection cavity as a non‐nodular, ring‐like enhancing structure. Both PP and TN lesions almost exclusively developed in the main prior radiation field. Presence of either condition appeared to be associated with above‐average overall survival. Conclusion: PP and TN occur in clinically distinct patient populations and exhibit differences in spatial radiographic pattern. Increased familiarity with both conditions and their unique features will improve patient management and may avoid unnecessary surgical procedures. Implications for Practice: Pseudoprogression (PP) and treatment‐induced brain tissue necrosis (TN) are challenging treatment‐related effects mimicking tumor progression in patients with brain cancer. Affected patients frequently require surgery to guide management. PP and TN remain arbitrarily defined and insufficiently characterized. Lack of clear diagnostic criteria compromises treatment and may adversely affect outcome interpretation in clinical trials. The present findings in a cohort of patients with glioma with PP/TN suggest that both phenomena exhibit unique clinical and imaging characteristics, manifest in different patient populations, and should be classified as distinct clinical conditions. Increased familiarity with PP and TN key features may guide clinicians toward timely noninvasive diagnosis, circumvent potentially unnecessary surgical procedures, and improve response assessment in neuro‐oncology. Cancer treatment–related adverse effects on the brain are a major diagnostic and therapeutic challenge in neuro‐oncology. This article describes the key clinical and imaging features of pseudoprogression and treatment‐induced brain tissue necrosis in patients with malignant glioma in an attempt to improve the current understanding of these conditions, facilitate the noninvasive diagnosis of treatment‐related adverse effects, and improve response assessment in neuro‐oncology. [ABSTRACT FROM AUTHOR]

Craniotomy for tumor resection improves survival in adults aged ≥65 years with malignant glioma. However, the decision to attempt resection must be weighed against the near-term risks of surgery. This study examined risk factors associated with unfavorable 30-day outcomes following craniotomy for malignant glioma resection in older adult patients. The American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2016 was queried for patients aged 65–89 years undergoing craniotomy for primary, supratentorial, malignant, intra-axial tumor resection. 30-day outcomes included mortality, life-threatening complication, unplanned readmission, reoperation, and change in living disposition. Independent risk factors were identified through multiple logistic regression. In total, 1016 cases met eligibility criteria. Death occurred in 35 cases (3.4%). 58 patients (5.7%) suffered at least one life-threatening complication. Risk factors for morbidity and mortality included frontal lobe tumor, corticosteroid use, dependent functional status, and underweight body mass index (BMI). Among 816 patients admitted from home, 33.9% experienced a change in living disposition, which was associated with advanced age, female sex, frontal lobe tumor, underweight BMI, and diabetes mellitus (among others). Readmission (11.8%) was most frequently attributed to altered mental status, seizure, or venous thromboembolism. Reoperation was rare (4.5%). Death and life-threatening morbidity were rare early outcomes for older adult patients undergoing malignant glioma resection. However, one in three patients admitted from home experienced a change in living disposition. Factors related to baseline state of health, tumor location, and corticosteroid regimen should be considered when anticipating the immediate postoperative course. [ABSTRACT FROM AUTHOR]

Recent research has revealed that glioblastoma (GBM) avoids the immune system via strong expression of indoleamine 2,3-dioxygenase 1 (IDO1). IDO1, an enzyme involved in tryptophan metabolism, is now proposed as a new target in GBM treatment, since several reports have demonstrated that IDO1 expression is related to GBM malignancy. On the other hand, it is well known that glioma stem cells (GSCs) are strongly related to the malignancy of GBM. However, there is as yet no report evaluating the relationship between GSCs and IDO1. We therefore examined the expression levels of IDO1 in GSCs in order to identify a new therapeutic target for GBM based on the immune systems of GSCs. In the present study, we employed human GBM cell lines (U-138MG, U-251MG) and patient-derived GSC model cell lines (0125-GSC, 0222-GSC). GSC model cell lines Rev-U-138MG and Rev-U-251MG were established by culturing U-138MG and U-251MG in serum-free media, while differentiated GBM model cell lines 0125-DGC and 0222-DGC were established by culturing 0125-GSC and 0222-GSC in serum-containing media. The expression levels of stem cell markers (Nanog, Nestin, Oct4 and Sox2) and IDO1 protein and mRNA were determined. Rev-U-138MG and Rev-U-251MG formed spheres and their expression levels of stem cell markers were increased as compared to U-138MG and U-251MG. On the other hand, 0125-DGC and 0222-DGC suffered breakdown of sphere formation, despite the original 0125-GSC and 0222-GSC forming spheres, and their expression levels of the markers were decreased. IDO1 expressions were strongly recognized in Rev-U-138MG, Rev-U-251MG, 0125-GSC and 0222-GSC as compared to U-138MG, U-251MG, 0125-DGC and 0222-DGC. These findings demonstrate that GSCs exhibit treatment resistance with immunosuppression via high expression levels of IDO1, and could represent a novel target for GBM treatment. • IDO1 is highly expressed in glioma stem cells. • Glioma stem cells suppress the immune system via IDO1 expression. • IDO1 expression is related to GBM differentiation state. [ABSTRACT FROM AUTHOR]

Background: The BLUE 400 filter system (Carl Zeiss Meditec, Oberkochen, Germany) has provided visualization of 5-ALA-induced fluorescence-guided surgery for more than 20 years. Nevertheless, constraints, e.g., limited background discrimination during hemostasis, obstruct fluency of surgery. A novel filter with improved background visualization was developed, requiring validation regarding fluorescence discrimination. The aim of this article is to determine diagnostic accuracy and perception of protoporphyrin IX (PpIX) discrimination of a novel filter system with higher background illumination (BLUE 400 AR) compared with the gold standard, BLUE 400. Methods: A surgical microscope equipped with both BLUE 400 and BLUE 400 AR was used. Comparisons were performed on a biological basis and on the visual perception of margins. High-resolution images were compared during and after surgery by senior neurosurgeons. In a predefined biopsy algorithm, four biopsies per patient at tumor margins of PpIX fluorescence and adjacent brain were acquired using BLUE 400 AR only from regions intended for resection and assessed for cell count and density. Results: Thirty-two patients with malignant gliomas were included in this study. BLUE 400 AR markedly enhanced the brightness of the surgical field, allowing superior discrimination of brain anatomy. A total of 128 biopsies from fluorescence margins were collected. Positive predictive value (PPV) was 98.44% (95% CI, 90.06–99.77%) for malignant glioma. Residual median cell density in non-fluorescent tissue was 13% (IQR 13 to 31). Perception of the location of fluorescent margins on HD images was equivalent for both filter combinations. Conclusions: BLUE 400 AR demonstrated superior background compared with conventional BLUE 400 in malignant glioma surgery but comparable fluorescence margins and PPV. Therefore, BLUE 400 AR can be considered safe and effective in supporting malignant glioma surgery. [ABSTRACT FROM AUTHOR]

Introduction: High hospital case volumes are associated with improved treatment outcomes for numerous diseases. We assessed the association between academic non-profit hospital case volume and survival of adult glioblastoma patients. Methods: From the nationwide Finnish Cancer Registry, we identified all adult (≥ 18 years) patients with histopathological diagnoses of glioblastoma from 2000 to 2013. Five university hospitals (treating all glioblastoma patients in Finland) were classified as high-volume (one hospital), middle-volume (one hospital), and low-volume (three hospitals) based on their annual numbers of cases. We estimated one-year survival rates, estimated median overall survival times, and compared relative excess risk (RER) of death between high, middle, and low-volume hospitals. Results: A total of 2,045 patients were included. The mean numbers of annually treated patients were 54, 40, and 17 in the high, middle, and low-volume hospitals, respectively. One-year survival rates and median survival times were higher and longer in the high-volume (39%, 9.3 months) and medium-volume (38%, 8.9 months) hospitals than in the low-volume (32%, 7.8 months) hospitals. RER of death was higher in the low-volume hospitals than in the high-volume hospital (RER = 1.19, 95% CI 1.07–1.32, p = 0.002). There was no difference in RER of death between the high-volume and medium-volume hospitals (p = 0.690). Conclusion: Higher glioblastoma case volumes were associated with improved survival. Future studies should assess whether this association is due to differences in patient-specific factors or treatment quality. [ABSTRACT FROM AUTHOR]

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As the most common primary malignant brain tumor with a devastating survival perspective, glioblastoma treatment remains a major challenge in medicine. Among recent approaches, 5-aminolevulnic acid (5-ALA) mediated interstitial photodynamic therapy (iPDT) has shown promising results. 16 patients with de-novo glioblastoma treated with iPDT were retrospectively analyzed regarding survival and characteristic tissue regions discernible in recorded MRI data. These regions were segmented at different stages and analyzed, especially regarding their impact on survival. The iPDT cohort showed a median progression-free survival (PFS) of 16.4 months and a median overall survival (OS) of 28.0 months. 10 of 16 patients experienced prolonged survival (≥ 24 months). In comparison to other therapies, the iPDT cohort maintained a significantly prolonged PFS and OS. Known prognostic factors for survival after standard treatment were not found to be relevant for this cohort, such as necrosis-tumor ratio, tumor volume and post-treatment contrast enhancement. In this study, iPDT has shown its potential, especially by a large fraction of prolonged survival. Prognosis-related parameters can be derived from patient data and MR imaging data, but their interpretation has to be adapted in comparison to standard-of-care. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to report a rare case of a pediatric pineal gliosarcoma. Gliomas on the pineal region are uncommon, representing 0.4%-1% of all brain tumors. Furthermore, pediatric gliosarcomas are a very rare entity. We present a case of a 5-year-old girl, with a history of headache, vomiting, diplopia, and gait disturbances. A pineal tumor was found with pathology results consistent with a gliosarcoma. A total of 25 cases of pediatric gliosarcomas have been reported, none of them in pineal topography. Only 3 gliosarcomas were found in the pineal region, but these were found in adults. To our knowledge, this is the first pediatric pineal gliosarcoma reported in the literature.

High-grade glioma (HGG) is a devastating disease with very poor prognosis. Maximal resection of HGG improves survival and maximal visualization of the tumor, if reliable, improves the resection. Fluorescence is widely used as guidance mechanism and has demonstrated potential in maximizing the extent of HGG resection. Our goal is to summarize the current techniques using fluorescence during the resection of HGG and demonstrate how its use increases gross total resection rates, overall survival (OS), and progression-free survival (PFS). However, further prospective, multicenter, randomized controlled trials are still in need to prove the advantage of fluorescence-guided surgery on patients' OS/PFS.

High-grade gliomas (HGGs) in pediatric age have the same bad prognosis as those arising in adults. Approximately one-half of HGGs in children occur in the brain stem, most frequently within the pons as diffuse intrinsic pontine glioma or other midline structures. Although they have the same histological appearance of adult malignant gliomas, in recent years, the extensive use of molecular profiling techniques has demonstrated significant molecular differences between the two age groups. These data have led to a major reclassification of pediatric HGG (pHGG) based on molecular subgrouping with significant clinical correlations in terms of age at presentation, anatomical location, and prognosis. The most important molecular groups are: (1) the histone mutations related pHGG, that is, H3.K27-mutated midline and H3.G34-mutated hemispheric pHGG; (2) the rare isocitrate dehydrogenase (IDH)-mutated pHGG occurring mainly in adolescents; and (3) the H3-/IDH wild type, a heterogenous group of pHGG still object of further molecular stratification. Another important group of pHGG is that occurring in patients with cancer predisposition syndromes such as Li-Fraumeni syndrome, constitutional mismatch repair deficiency, and neurofibromatosis-1 (NF1). In this review, the different subgroups of pHGG and their major driver molecular alterations will be discussed.

Interpretation of MRI abnormalities in patients with malignant gliomas (MG) treated with bevacizumab is challenging. Recent reports describe quantitative analyses of diffusion-weighted imaging abnormalities not available in standard clinical settings, to differentiate tumor recurrence from treatment necrosis. We retrospectively reviewed bevacizumab treated MG patients who underwent surgery or autopsy to correlate radiographic recurrence patterns with pathologic findings. 32 patients with MG (26 glioblastoma, three anaplastic astrocytoma and three anaplastic oligodendroglioma) were identified. Recurrence patterns: local enhancing (n = 23), distant enhancing (n = 1), nonenhancing (n = 7) and leptomeningeal (n = 1). Histology: tumor (n = 25), mixed tumor/necrosis (n = 5) and all necrosis (n = 2). On diffusion-weighted imaging, 5/32 had restricted diffusion (three mixed and two necrosis). Irrespective of radiographic recurrence pattern, tumor was found in 94% of cases. Restricted diffusion correlated with necrosis.

Chaofeng Liang,1,* Weitong Sun,2,* Haiyong He,1,* Baoyu Zhang,1 Cong Ling,1 Bocheng Wang,1 Tengchao Huang,1 Bo Hou,1 Ying Guo1 1Department of Neurosurgery, 3rd Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangdong, China; 2The Pharmaceutical College of Jiamusi University, Jiamusi University, Jiamusi, China *These authors contributed equally to this work Introduction: MiR-135a is found to selectively induce apoptosis in glioma cell but not in normal neurons and glial cells. However, low transfection efficacy limits its application in vivo as other miRNAs. We prepared a new kind of nano-vector based on polyethylene glycol methyl ether (mPEG) and hyper-branched polyethylenimine (hy-PEI) in order to improve the miRNA delivery system into the glioma cells. Methods: The mPEG-g-PEI/miR-135a was constructed and detected by 1H NMR and FTIR analyses. Transmission electron microscope was utilized for its characteristics. Stability and release efficiency was assessed by electrophoresis. Biocompatibility was observed and analyzed through co-culture with astrocytes and malignant glioma cells (C6). Transfection rate was monitored by laser confocal microscopy and flow cytometry. The antitumor effect of mPEG-g-PEI/miR-135a to C6 was confirmed in vivo by MR scanning, pathology and survival curve. RT-PCR was used to assay transfection efficiency of mPEG-g-PEI/miR-135a in vitro and in vivo. And Western blotting was used to assess the expressions of the targeted proteins of miR-135a.Results: In this experiment, we found the optimal N/P ratio of mPEG-g-PEI/miR-135a was about 6 judged by Zeta potential, particle size and encapsulation ability. The stability of mPEG-g-PEI/miR-135a in serum and the release efficiency in acid(pH=5.0) of mPEG-g-PEI/miR-135a were simulated the environment in vivo and in tumor. The mPEG-g-PEI nano-vector was co-cultured with malignant glioma cell C6 and normal astrocytes in vitro and showed good biocompatibility evaluated by CCK8 assay. The cell experiments in vitro indicated that mPEG-g-PEI could significantly improve miR-135a transfection by enhancing uptake effect of both normal glial and glioma cells. Given the C6 implanted in situ model, we discovered that the mPEG-g-PEI/miR-135a could obviously increase the survival period and inhibit the growth of glioma confirmed by MRI and histochemistry. In addition, the transfection efficiency of mPEG-g-PEI was better than that of other transfection agents either in vitro or in vivo confirmed by RT-PCR. Moreover, the expressions of the targeted proteins of miR-135a were consistent with the in vitro results. Conclusion: These results suggest that mPEG-g-PEI is expected to provide a new effective intracellular miRNA delivery system with low toxicity for glioma therapy. Keywords: nano-vector, miRNA-135a, malignant glioma, gene delivery, Micro RNA