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Brain Sciences
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Advance in Glioma Invasion
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Advance in Glioma Invasion

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Neuro-oncology".

Deadline for manuscript submissions: closed (6 March 2022) | Viewed by 22002

Special Issue Editor

Prof. Dr. Takanori Ohnishi

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Guest Editor
Department of Neurosurgery, Washoukai Sadamoto Hospital, Advanced Brain Disease Center (Director), Matsuyama, Ehime, Japan
Interests: glioma; glioblastoma; invasion; glioma stem-like cells; glioma metabolism; neuroimaging; sonodynamic therapy; neurosurgery; neuro-oncology

Special Issue Information

Dear Colleagues,

The poor prognosis of glioblastoma (GBM) is due, in part, to glioma stem-like cells (GSCs), which constitute a subpopulation of tumor cells in GBM and characteristically show high invasiveness and resistance to radio-chemotherapy. GSCs reside in a hypoxic microenvironment called the “niche” and are thought to regulate dynamically tumor proliferation, invasion, and angiogenesis through the intricate crosstalk between GSCs and non-tumor cells and various components of the microenvironment. Particularly, hypoxia and acidic environments enhance the invasiveness of GSCs much more, and the highly invasive GSCs may escape from even maximum resection of the tumor and aggressively proliferate to generate early tumor recurrence. Consequently, eradication of GSCs will significantly improve the prognosis of the patients with GBM. The aim of this Special Issue is to deepen our understanding of the significance of highly invasive GSCs under a special microenvironment on tumor progression and recurrence in GBM and to find a cue to develop a novel therapeutic method against tumor invasion. Aiming for a significant advance in the research and therapy of malignant gliomas through this Special Issue, we seek manuscripts of cutting-edge research in the broad fields from basic neuroscience to clinical neuroscience concerning glioma invasion. The areas include molecular and cellular neuroscience in neuro-oncology, clinical neuroscience, and neuroimaging of malignant brain tumors. We would like to encourage you to submit to this Special Issue, in which the topic is focused on “glioma invasion”, your original research articles, review articles, and short communications of preliminary results. We look forward to receiving your contributions.

Prof. Dr. Takanori Ohnishi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • glioma
  • glioblastoma
  • invasion
  • cancer stem cells
  • glioma stem-like cells
  • niches
  • tumor microenvironment
  • hypoxia
  • tumor recurrence
  • survival

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Published Papers (7 papers)

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Editorial

Jump to: Research, Review

7 pages, 671 KiB  
Editorial
Current Status and Future Perspective in Glioma Invasion Research
by Takanori Ohnishi
Brain Sci. 2024, 14(4), 309; https://doi.org/10.3390/brainsci14040309 - 26 Mar 2024
Cited by 2 | Viewed by 1248
Abstract
Glioblastoma (GBM) is the most malignant brain tumor in adults and shows an extremely poor prognosis, with a median survival of 15 months [...] Full article
(This article belongs to the Special Issue Advance in Glioma Invasion)
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Research

Jump to: Editorial, Review

21 pages, 16297 KiB  
Article
Orthotopic Transplantation of Human Paediatric High-Grade Glioma in Zebrafish Larvae
by Susanna Larsson, Petronella Kettunen and Helena Carén
Brain Sci. 2022, 12(5), 625; https://doi.org/10.3390/brainsci12050625 - 10 May 2022
Viewed by 2609
Abstract
Brain tumours are the most common cause of death among children with solid tumours, and high-grade gliomas (HGG) are among the most devastating forms with very poor outcomes. In the search for more effective treatments for paediatric HGG, there is a need for [...] Read more.
Brain tumours are the most common cause of death among children with solid tumours, and high-grade gliomas (HGG) are among the most devastating forms with very poor outcomes. In the search for more effective treatments for paediatric HGG, there is a need for better experimental models. To date, there are no xenograft zebrafish models developed for human paediatric HGG; existing models rely on adult cells. The use of paediatric models is of great importance since it is well known that the genetic and epigenetic mechanisms behind adult and paediatric disease differ greatly. In this study, we present a clinically relevant in vivo model based on paediatric primary glioma stem cell (GSC) cultures, which after orthotopic injection into the zebrafish larvae, can be monitored using confocal imaging over time. We show that cells invade the brain tissue and can be followed up to 8 days post-injection while they establish in the fore/mid brain. This model offers an in vivo system where tumour invasion can be monitored and drug treatments quickly be evaluated. The possibility to monitor patient-specific cells has the potential to contribute to a better understanding of cellular behaviour and personalised treatments in the future. Full article
(This article belongs to the Special Issue Advance in Glioma Invasion)
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Graphical abstract

17 pages, 2870 KiB  
Article
Is Interstitial Chemotherapy with Carmustine (BCNU) Wafers Effective against Local Recurrence of Glioblastoma? A Pharmacokinetic Study by Measurement of BCNU in the Tumor Resection Cavity
by Takanori Ohnishi, Daisuke Yamashita, Akihiro Inoue, Satoshi Suehiro, Shiro Ohue and Takeharu Kunieda
Brain Sci. 2022, 12(5), 567; https://doi.org/10.3390/brainsci12050567 - 28 Apr 2022
Cited by 7 | Viewed by 2309
Abstract
The effectiveness of carmustine (BCNU) wafers on local recurrence of glioblastoma (GBM) remains contentious. We investigated the accumulating high-dose effects of BCNU released from the wafers on the survival of GBM patients by measuring BCNU concentration in the resection cavity of GBM over [...] Read more.
The effectiveness of carmustine (BCNU) wafers on local recurrence of glioblastoma (GBM) remains contentious. We investigated the accumulating high-dose effects of BCNU released from the wafers on the survival of GBM patients by measuring BCNU concentration in the resection cavity of GBM over time. BCNU wafers (Gliadel®) were implanted with an Ommaya device in 15 patients, including 12 patients with GBM. BCNU concentrations in the tumor resection cavity were measured for 30 days postoperatively. The area under the curve (AUC)all was calculated from BCNU concentration curves, and the relationships between AUCall and survival, tumor phenotypes on MRI, and recurrence patterns were analyzed. The BCNU concentration was maximal 1 h postoperatively, rapidly decreased within 24 h, and remained relatively high for 7 days. GBM patients were classified into two groups: early recurrence (ER) and late or no recurrence (LN), using median progression-free survival as the cut-off. AUCall tended to be lower in the ER group than in the LN group, but the difference was not significant. MRI revealed that all patients in the ER group had highly invasive GBMs, whereas all patients in the LN group had less-invasive GBMs. A total of 9 patients experienced recurrence, with 6 local, 2 diffuse, and 1 disseminated patterns. No differences in AUCall were seen between local and non-local recurrence groups. Total BCNU concentrations did not correlate with tumor progression or survival. However, a high concentration of BCNU may have potential to provide some survival benefit for less-invasive type GBM. Full article
(This article belongs to the Special Issue Advance in Glioma Invasion)
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9 pages, 2149 KiB  
Communication
Prediction and Visualization of Non-Enhancing Tumor in Glioblastoma via T1w/T2w-Ratio Map
by Shota Yamamoto, Takahiro Sanada, Mio Sakai, Atsuko Arisawa, Naoki Kagawa, Eku Shimosegawa, Katsuyuki Nakanishi, Yonehiro Kanemura, Manabu Kinoshita and Haruhiko Kishima
Brain Sci. 2022, 12(1), 99; https://doi.org/10.3390/brainsci12010099 - 12 Jan 2022
Cited by 5 | Viewed by 2318
Abstract
One of the challenges in glioblastoma (GBM) imaging is to visualize non-enhancing tumor (NET) lesions. The ratio of T1- and T2-weighted images (rT1/T2) is reported as a helpful imaging surrogate of microstructures of the brain. This research study investigated the possibility of using [...] Read more.
One of the challenges in glioblastoma (GBM) imaging is to visualize non-enhancing tumor (NET) lesions. The ratio of T1- and T2-weighted images (rT1/T2) is reported as a helpful imaging surrogate of microstructures of the brain. This research study investigated the possibility of using rT1/T2 as a surrogate for the T1- and T2-relaxation time of GBM to visualize NET effectively. The data of thirty-four histologically confirmed GBM patients whose T1-, T2- and contrast-enhanced T1-weighted MRI and 11C-methionine positron emission tomography (Met-PET) were available were collected for analysis. Two of them also underwent MR relaxometry with rT1/T2 reconstructed for all cases. Met-PET was used as ground truth with T2-FLAIR hyperintense lesion, with >1.5 in tumor-to-normal tissue ratio being NET. rT1/T2 values were compared with MR relaxometry and Met-PET. rT1/T2 values significantly correlated with both T1- and T2-relaxation times in a logarithmic manner (p < 0.05 for both cases). The distributions of rT1/T2 from Met-PET high and low T2-FLAIR hyperintense lesions were different and a novel metric named Likeliness of Methionine PET high (LMPH) deriving from rT1/T2 was statistically significant for detecting Met-PET high T2-FLAIR hyperintense lesions (mean AUC = 0.556 ± 0.117; p = 0.01). In conclusion, this research study supported the hypothesis that rT1/T2 could be a promising imaging marker for NET identification. Full article
(This article belongs to the Special Issue Advance in Glioma Invasion)
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Review

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28 pages, 18716 KiB  
Review
Tumor Microenvironment in Glioma Invasion
by Sho Tamai, Toshiya Ichinose, Taishi Tsutsui, Shingo Tanaka, Farida Garaeva, Hemragul Sabit and Mitsutoshi Nakada
Brain Sci. 2022, 12(4), 505; https://doi.org/10.3390/brainsci12040505 - 15 Apr 2022
Cited by 35 | Viewed by 5796
Abstract
A major malignant trait of gliomas is their remarkable infiltration capacity. When glioma develops, the tumor cells have already reached the distant part. Therefore, complete removal of the glioma is impossible. Recently, research on the involvement of the tumor microenvironment in glioma invasion [...] Read more.
A major malignant trait of gliomas is their remarkable infiltration capacity. When glioma develops, the tumor cells have already reached the distant part. Therefore, complete removal of the glioma is impossible. Recently, research on the involvement of the tumor microenvironment in glioma invasion has advanced. Local hypoxia triggers cell migration as an environmental factor. The transcription factor hypoxia-inducible factor (HIF) -1α, produced in tumor cells under hypoxia, promotes the transcription of various invasion related molecules. The extracellular matrix surrounding tumors is degraded by proteases secreted by tumor cells and simultaneously replaced by an extracellular matrix that promotes infiltration. Astrocytes and microglia become tumor-associated astrocytes and glioma-associated macrophages/microglia, respectively, in relation to tumor cells. These cells also promote glioma invasion. Interactions between glioma cells actively promote infiltration of each other. Surgery, chemotherapy, and radiation therapy transform the microenvironment, allowing glioma cells to invade. These findings indicate that the tumor microenvironment may be a target for glioma invasion. On the other hand, because the living body actively promotes tumor infiltration in response to the tumor, it is necessary to reconsider whether the invasion itself is friend or foe to the brain. Full article
(This article belongs to the Special Issue Advance in Glioma Invasion)
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Graphical abstract

14 pages, 1322 KiB  
Review
A Tumor Suppressor Gene, N-myc Downstream-Regulated Gene 1 (NDRG1), in Gliomas and Glioblastomas
by Yukiko Nakahara, Hiroshi Ito, Hiroki Namikawa, Takashi Furukawa, Fumitaka Yoshioka, Atsushi Ogata, Jun Masuoka and Tatsuya Abe
Brain Sci. 2022, 12(4), 473; https://doi.org/10.3390/brainsci12040473 - 3 Apr 2022
Cited by 6 | Viewed by 3289
Abstract
The development of potent and selective therapeutic approaches to glioblastoma (GBM) requires the identification of molecular pathways that critically regulate the survival and proliferation of GBM. Glioblastoma stem-like cells (GSCs) possess stem-cell-like properties, self-renewal, and differentiation into multiple neural cell lineages. From a [...] Read more.
The development of potent and selective therapeutic approaches to glioblastoma (GBM) requires the identification of molecular pathways that critically regulate the survival and proliferation of GBM. Glioblastoma stem-like cells (GSCs) possess stem-cell-like properties, self-renewal, and differentiation into multiple neural cell lineages. From a clinical point of view, GSCs have been reported to resist radiation and chemotherapy. GSCs are influenced by the microenvironment, especially the hypoxic condition. N-myc downstream-regulated gene 1 (NDRG1) is a tumor suppressor with the potential to suppress the proliferation, invasion, and migration of cancer cells. Previous studies have reported that deregulated expression of NDRG1 affects tumor growth and clinical outcomes of patients with GBM. This literature review aimed to clarify the critical role of NDRG1 in tumorigenesis and acquirement of resistance for anti-GBM therapies, further to discussing the possibility and efficacy of NDRG1 as a novel target of treatment for GBM. The present review was conducted by searching the PubMed and Scopus databases. The search was conducted in February 2022. We review current knowledge on the regulation and signaling of NDRG1 in neuro-oncology. Finally, the role of NDRG1 in GBM and potential clinical applications are discussed. Full article
(This article belongs to the Special Issue Advance in Glioma Invasion)
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18 pages, 1578 KiB  
Review
Molecular Mechanisms and Clinical Challenges of Glioma Invasion
by Tomoya Oishi, Shinichiro Koizumi and Kazuhiko Kurozumi
Brain Sci. 2022, 12(2), 291; https://doi.org/10.3390/brainsci12020291 - 20 Feb 2022
Cited by 14 | Viewed by 3312
Abstract
Glioma is the most common primary brain tumor, and its prognosis is poor. Glioma cells are highly invasive to the brain parenchyma. It is difficult to achieve complete resection due to the nature of the brain tissue, and tumors that invade the parenchyma [...] Read more.
Glioma is the most common primary brain tumor, and its prognosis is poor. Glioma cells are highly invasive to the brain parenchyma. It is difficult to achieve complete resection due to the nature of the brain tissue, and tumors that invade the parenchyma often recur. The invasiveness of tumor cells has been studied from various aspects, and the related molecular mechanisms are gradually becoming clear. Cell adhesion factors and extracellular matrix factors have a strong influence on glioma invasion. The molecular mechanisms that enhance the invasiveness of glioma stem cells, which have been investigated in recent years, have also been clarified. In addition, it has been discussed from both basic and clinical perspectives that current therapies can alter the invasiveness of tumors, and there is a need to develop therapeutic approaches to glioma invasion in the future. In this review, we will summarize the factors that influence the invasiveness of glioma based on the environment of tumor cells and tissues, and describe the impact of the treatment of glioma on invasion in terms of molecular biology, and the novel therapies for invasion that are currently being developed. Full article
(This article belongs to the Special Issue Advance in Glioma Invasion)
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