Special Issue "Glioblastoma"

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A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 June 2013)

Special Issue Editors

Guest Editor
Prof. Dr. Shi-Yuan Cheng

Department of Neurology, Northwestern Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center University of Northwestern Feinberg School of Medicine, 303 East Superior, Lurie 7-119, Chicago, IL 60026, USA
Website | E-Mail
Interests: oncogenic signaling; glioblastomas; breast cancers; cancer biology; molecular mechanisms of human cancer tumorigenesis, progression, invasion/metastasis and angiogenesis
Guest Editor
Prof. Dr. Frank Furnari

Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093-0660, USA
Website | E-Mail
Fax: +1 858 534 7750
Interests: glioma; tumor heterogeneity; EGFR; PTEN; targeted therapeutics; receptor tyrosine kinases

Special Issue Information

Dear Colleagues,

Neoplasms of glial cells, especially astrocytes, comprise 40-50% of the tumors that arise in the central nervous system. The most aggressive and deadly of these neoplasms is glioblastoma multiforme (GBM). Despite rapidly increasing knowledge of the gliomagenic lesions that underlie these tumor phenotypes and decades of technological advances in neurosurgery, radiation therapy and clinical trials of conventional and novel therapies, little improvement in the median survival of 12-15 months has been achieved for GBM patients. Therefore, it is essential and urgent that we improve our current knowledge of the molecular and cellular mechanisms of GBM initiation, progression and resistance to therapy. This special issue will focus on new advances in the molecular and cellular aspects of the pathophysiology of GBM and novel therapeutic approaches to eradicate this deadly brain cancer.
We are looking forward to your contributions.

Prof. Dr. Shi-Yuan Cheng
Prof. Dr. Frank Furnari
Guest Editors

Submission

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Keywords

  • molecular mechanisms of gliomagenesis and progression and therapy resistance
  • glioma stem cells
  • cancer metabolism
  • therapies for malignant gliomas
  • pathology/genomics
  • miRNAs
  • glioma tumor heterogeneity

Published Papers (15 papers)

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Research

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Open AccessArticle Three-Times Daily Ultrafractionated Radiation Therapy, A Novel and Promising Regimen for Glioblastoma Patients
Cancers 2013, 5(4), 1199-1211; doi:10.3390/cancers5041199
Received: 5 August 2013 / Revised: 16 August 2013 / Accepted: 18 August 2013 / Published: 25 September 2013
Cited by 4 | PDF Full-text (559 KB) | HTML Full-text | XML Full-text
Abstract
Glioblastomas are considered to be one of the most radio resistant tumors. Despite new therapies, the prognosis of this disease remains dismal. Also, the mechanisms of radiation resistance in mammalian cells are more complex than once believed. Experimental studies have indicated that some
[...] Read more.
Glioblastomas are considered to be one of the most radio resistant tumors. Despite new therapies, the prognosis of this disease remains dismal. Also, the mechanisms of radiation resistance in mammalian cells are more complex than once believed. Experimental studies have indicated that some human cell lines are sensitive to low radiation doses of <1 Gy. This phenomenon has been termed low-dose hyper-radio-sensitivity (HRS), and is more apparent in radio resistant cell lines, such as glioblastoma cells. Sensitivity may result from the inability of low dose radiation to efficiently induce repair mechanisms, whereas higher doses cause enough damage to trigger repair responses for radio resistance. In vitro studies have demonstrated this phenomenon using various human malignant glioma cell lines: (1) daily repeated irradiation of cells with low doses compared to irradiation using a single biologically equivalent dose resulted in significantly higher cell killing; (2) experiments conducted on glioma xenografts demonstrated that repeated irradiation with low doses was more effective for inhibiting tumor growth than a single dose. In order to confirm and validate these promising studies on HRS, a few phase II trials were developed. For translating the experimental observations into the clinic, ultra fractionation protocols (with three daily doses) were tested in glioblastoma patients. Tolerance and toxicity were the primary endpoints, with overall survival as a secondary endpoint. These protocols were initiated before concomitant radio chemotherapy became the standard of care. For these trials, patients with an unfavorable clinical prognostic factor of newly unresectable GBM were included. When comparing the results of these trials with international literature using multivariate analysis for both progression free survival and overall survival, ultra fractionated irradiation showed superiority over radiotherapy alone. In addition, it was found to be equivalent to treatment using radiotherapy and temozolomide. Therefore, ultra fractionated protocols may prolong survival of glioblastoma patients. In this review, we describe the main experimental data regarding low-dose hypersensitivity as well as the findings of clinical trials that have investigated this new radiotherapy regimen. Full article
(This article belongs to the Special Issue Glioblastoma)
Open AccessArticle Outcomes in Newly Diagnosed Elderly Glioblastoma Patients after Concomitant Temozolomide Administration and Hypofractionated Radiotherapy
Cancers 2013, 5(3), 1177-1198; doi:10.3390/cancers5031177
Received: 1 July 2013 / Revised: 12 August 2013 / Accepted: 10 September 2013 / Published: 24 September 2013
Cited by 7 | PDF Full-text (593 KB) | HTML Full-text | XML Full-text
Abstract
This study aimed to analyze the treatment and outcomes of older glioblastoma patients. Forty-four patients older than 70 years of age were referred to the Paul Strauss Center for chemotherapy and radiotherapy. The median age was 75.5 years old (range: 70–84), and the
[...] Read more.
This study aimed to analyze the treatment and outcomes of older glioblastoma patients. Forty-four patients older than 70 years of age were referred to the Paul Strauss Center for chemotherapy and radiotherapy. The median age was 75.5 years old (range: 70–84), and the patients included 18 females and 26 males. The median Karnofsky index (KI) was 70%. The Charlson indices varied from 4 to 6. All of the patients underwent surgery. O6-methylguanine–DNA methyltransferase (MGMT) methylation status was determined in 25 patients. All of the patients received radiation therapy. Thirty-eight patients adhered to a hypofractionated radiation therapy schedule and six patients to a normofractionated schedule. Neoadjuvant, concomitant and adjuvant chemotherapy regimens were administered to 12, 35 and 20 patients, respectively. At the time of this analysis, 41 patients had died. The median time to relapse was 6.7 months. Twenty-nine patients relapsed, and 10 patients received chemotherapy upon relapse. The median overall survival (OS) was 7.2 months and the one- and two-year OS rates were 32% and 12%, respectively. In a multivariate analysis, only the Karnofsky index was a prognostic factor. Hypofractionated radiotherapy and chemotherapy with temozolomide are feasible and acceptably tolerated in older patients. However, relevant prognostic factors are needed to optimize treatment proposals. Full article
(This article belongs to the Special Issue Glioblastoma)
Open AccessArticle Glioma Surgical Aspirate: A Viable Source of Tumor Tissue for Experimental Research
Cancers 2013, 5(2), 357-371; doi:10.3390/cancers5020357
Received: 18 February 2013 / Revised: 18 March 2013 / Accepted: 22 March 2013 / Published: 3 April 2013
Cited by 8 | PDF Full-text (1300 KB) | HTML Full-text | XML Full-text
Abstract
Brain cancer research has been hampered by a paucity of viable clinical tissue of sufficient quality and quantity for experimental research. This has driven researchers to rely heavily on long term cultured cells which no longer represent the cancers from which they were
[...] Read more.
Brain cancer research has been hampered by a paucity of viable clinical tissue of sufficient quality and quantity for experimental research. This has driven researchers to rely heavily on long term cultured cells which no longer represent the cancers from which they were derived. Resection of brain tumors, particularly at the interface between normal and tumorigenic tissue, can be carried out using an ultrasonic surgical aspirator (CUSA) that deposits liquid (blood and irrigation fluid) and resected tissue into a sterile bottle for disposal. To determine the utility of CUSA-derived glioma tissue for experimental research, we collected 48 CUSA specimen bottles from glioma patients and analyzed both the solid tissue fragments and dissociated tumor cells suspended in the liquid waste fraction. We investigated if these fractions would be useful for analyzing tumor heterogeneity, using IHC and multi-parameter flow cytometry; we also assessed culture generation and orthotopic xenograft potential. Both cell sources proved to be an abundant, highly viable source of live tumor cells for cytometric analysis, animal studies and in-vitro studies. Our findings demonstrate that CUSA tissue represents an abundant viable source to conduct experimental research and to carry out diagnostic analyses by flow cytometry or other molecular diagnostic procedures. Full article
(This article belongs to the Special Issue Glioblastoma)

Review

Jump to: Research

Open AccessReview The Future of Glioblastoma Therapy: Synergism of Standard of Care and Immunotherapy
Cancers 2014, 6(4), 1953-1985; doi:10.3390/cancers6041953
Received: 2 June 2014 / Revised: 5 August 2014 / Accepted: 3 September 2014 / Published: 29 September 2014
Cited by 22 | PDF Full-text (687 KB) | HTML Full-text | XML Full-text
Abstract
The current standard of care for glioblastoma (GBM) is maximal surgical resection with adjuvant radiotherapy and temozolomide (TMZ). As the 5-year survival with GBM remains at a dismal <10%, novel therapies are needed. Immunotherapies such as the dendritic cell (DC) vaccine, heat shock
[...] Read more.
The current standard of care for glioblastoma (GBM) is maximal surgical resection with adjuvant radiotherapy and temozolomide (TMZ). As the 5-year survival with GBM remains at a dismal <10%, novel therapies are needed. Immunotherapies such as the dendritic cell (DC) vaccine, heat shock protein vaccines, and epidermal growth factor receptor (EGFRvIII) vaccines have shown encouraging results in clinical trials, and have demonstrated synergistic effects with conventional therapeutics resulting in ongoing phase III trials. Chemoradiation has been shown to have synergistic effects when used in combination with immunotherapy. Cytotoxic ionizing radiation is known to trigger pro-inflammatory signaling cascades and immune activation secondary to cell death, which can then be exploited by immunotherapies. The future of GBM therapeutics will involve finding the place for immunotherapy in the current treatment regimen with a focus on developing strategies. Here, we review current GBM therapy and the evidence for combination of immune checkpoint inhibitors, DC and peptide vaccines with the current standard of care. Full article
(This article belongs to the Special Issue Glioblastoma)
Open AccessReview Reciprocal Supportive Interplay between Glioblastoma and Tumor-Associated Macrophages
Cancers 2014, 6(2), 723-740; doi:10.3390/cancers6020723
Received: 13 February 2014 / Revised: 13 March 2014 / Accepted: 14 March 2014 / Published: 26 March 2014
Cited by 5 | PDF Full-text (353 KB) | HTML Full-text | XML Full-text
Abstract
Glioblastoma multiforme (GBM) is the most lethal and aggressive type of primary brain malignancy. Failures of the traditional therapies in treating GBMs raise the urgent requirement to develop new approaches with more responsive targets. The phenomenon of the high infiltration of tumor-associated macrophages
[...] Read more.
Glioblastoma multiforme (GBM) is the most lethal and aggressive type of primary brain malignancy. Failures of the traditional therapies in treating GBMs raise the urgent requirement to develop new approaches with more responsive targets. The phenomenon of the high infiltration of tumor-associated macrophages (TAMs) into GBMs has been observed for a long time. Regardless of the limited knowledge about TAMs, the high percentage of supportive TAM in GBM tumor mass makes it possible to be a good target for GBM treatment. In this review, we discussed the unique features of TAMs in GBMs, including their origin, the tumor-supportive properties, the secreted cytokines, and the relevant mechanisms. In addition, we tried to interpret the current understandings about the interplay between GBM cancer cells and TAMs. Finally, the translational studies of targeting TAMs were also described. Full article
(This article belongs to the Special Issue Glioblastoma)
Open AccessReview Glioblastoma Multiforme: A Look Inside Its Heterogeneous Nature
Cancers 2014, 6(1), 226-239; doi:10.3390/cancers6010226
Received: 1 November 2013 / Revised: 23 December 2013 / Accepted: 9 January 2014 / Published: 27 January 2014
Cited by 18 | PDF Full-text (471 KB) | HTML Full-text | XML Full-text
Abstract
Heterogeneity is a hallmark of tumors and has a crucial role in the outcome of the malignancy, because it not only confounds diagnosis, but also challenges the design of effective therapies. There are two types of heterogeneity: inter-tumor and intra-tumor heterogeneity. While inter-tumor
[...] Read more.
Heterogeneity is a hallmark of tumors and has a crucial role in the outcome of the malignancy, because it not only confounds diagnosis, but also challenges the design of effective therapies. There are two types of heterogeneity: inter-tumor and intra-tumor heterogeneity. While inter-tumor heterogeneity has been studied widely, intra-tumor heterogeneity has been neglected even though numerous studies support this aspect of tumor pathobiology. The main reason has been the technical difficulties, but with new advances in single-cell technology, intra-tumor heterogeneity is becoming a key area in the study of cancer. Several models try to explain the origin and maintenance of intra-tumor heterogeneity, however, one prominent model compares cancer with a tree where the ubiquitous mutations compose the trunk and mutations present in subpopulations of cells are represented by the branches. In this review we will focus on the intra-tumor heterogeneity of glioblastoma multiforme (GBM), the most common brain tumor in adults that is characterized by a marked heterogeneity at the cellular and molecular levels. Better understanding of this heterogeneity will be essential to design effective therapies against this devastating disease to avoid tumor escape. Full article
(This article belongs to the Special Issue Glioblastoma)
Open AccessReview Tumor Metabolism of Malignant Gliomas
Cancers 2013, 5(4), 1469-1484; doi:10.3390/cancers5041469
Received: 22 October 2013 / Accepted: 24 October 2013 / Published: 8 November 2013
Cited by 12 | PDF Full-text (530 KB) | HTML Full-text | XML Full-text
Abstract
Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming
[...] Read more.
Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a novel direction for drug development in oncology. In malignant gliomas, metabolism pathways of glucose, glutamine and lipid are significantly reprogrammed. Moreover, molecular mechanisms causing these metabolic changes are just starting to be unraveled. In this review, we will summarize recent studies revealing critical gene alterations that lead to metabolic changes in malignant gliomas, and also discuss promising therapeutic strategies via targeting the key players in metabolic regulation. Full article
(This article belongs to the Special Issue Glioblastoma)
Open AccessReview Bevacizumab for Glioblastoma—A Promising Drug or Not?
Cancers 2013, 5(4), 1456-1468; doi:10.3390/cancers5041456
Received: 11 October 2013 / Accepted: 24 October 2013 / Published: 7 November 2013
Cited by 2 | PDF Full-text (343 KB) | HTML Full-text | XML Full-text
Abstract
Two double blind, placebo-controlled, and randomized phase III studies were conducted, and the results including OS’s were reported at the ASCO Meeting in June 2013, which was the beginning of confusion surrounding this topic. This is a review article not only summarizing the
[...] Read more.
Two double blind, placebo-controlled, and randomized phase III studies were conducted, and the results including OS’s were reported at the ASCO Meeting in June 2013, which was the beginning of confusion surrounding this topic. This is a review article not only summarizing the previous evidence, but also looking beyond. Full article
(This article belongs to the Special Issue Glioblastoma)
Open AccessReview Immune-Checkpoint Blockade and Active Immunotherapy for Glioma
Cancers 2013, 5(4), 1379-1412; doi:10.3390/cancers5041379
Received: 16 September 2013 / Revised: 24 October 2013 / Accepted: 24 October 2013 / Published: 1 November 2013
Cited by 9 | PDF Full-text (573 KB) | HTML Full-text | XML Full-text
Abstract
Cancer immunotherapy has made tremendous progress, including promising results in patients with malignant gliomas. Nonetheless, the immunological microenvironment of the brain and tumors arising therein is still believed to be suboptimal for sufficient antitumor immune responses for a variety of reasons, including the
[...] Read more.
Cancer immunotherapy has made tremendous progress, including promising results in patients with malignant gliomas. Nonetheless, the immunological microenvironment of the brain and tumors arising therein is still believed to be suboptimal for sufficient antitumor immune responses for a variety of reasons, including the operation of “immune-checkpoint” mechanisms. While these mechanisms prevent autoimmunity in physiological conditions, malignant tumors, including brain tumors, actively employ these mechanisms to evade from immunological attacks. Development of agents designed to unblock these checkpoint steps is currently one of the most active areas of cancer research. In this review, we summarize recent progresses in the field of brain tumor immunology with particular foci in the area of immune-checkpoint mechanisms and development of active immunotherapy strategies. In the last decade, a number of specific monoclonal antibodies designed to block immune-checkpoint mechanisms have been developed and show efficacy in other cancers, such as melanoma. On the other hand, active immunotherapy approaches, such as vaccines, have shown encouraging outcomes. We believe that development of effective immunotherapy approaches should ultimately integrate those checkpoint-blockade agents to enhance the efficacy of therapeutic approaches. With these agents available, it is going to be quite an exciting time in the field. The eventual success of immunotherapies for brain tumors will be dependent upon not only an in-depth understanding of immunology behind the brain and brain tumors, but also collaboration and teamwork for the development of novel trials that address multiple layers of immunological challenges in gliomas. Full article
(This article belongs to the Special Issue Glioblastoma)
Open AccessReview Strategies in Gene Therapy for Glioblastoma
Cancers 2013, 5(4), 1271-1305; doi:10.3390/cancers5041271
Received: 3 October 2013 / Accepted: 15 October 2013 / Published: 23 October 2013
Cited by 12 | PDF Full-text (1466 KB) | HTML Full-text | XML Full-text
Abstract
Glioblastoma (GBM) is the most aggressive form of brain cancer, with a dismal prognosis and extremely low percentage of survivors. Novel therapies are in dire need to improve the clinical management of these tumors and extend patient survival. Genetic therapies for GBM have
[...] Read more.
Glioblastoma (GBM) is the most aggressive form of brain cancer, with a dismal prognosis and extremely low percentage of survivors. Novel therapies are in dire need to improve the clinical management of these tumors and extend patient survival. Genetic therapies for GBM have been postulated and attempted for the past twenty years, with variable degrees of success in pre-clinical models and clinical trials. Here we review the most common approaches to treat GBM by gene therapy, including strategies to deliver tumor-suppressor genes, suicide genes, immunomodulatory cytokines to improve immune response, and conditionally-replicating oncolytic viruses. The review focuses on the strategies used for gene delivery, including the most common and widely used vehicles (i.e., replicating and non-replicating viruses) as well as novel therapeutic approaches such as stem cell-mediated therapy and nanotechnologies used for gene delivery. We present an overview of these strategies, their targets, different advantages, and challenges for success. Finally, we discuss the potential of gene therapy-based strategies to effectively attack such a complex genetic target as GBM, alone or in combination with conventional therapy. Full article
(This article belongs to the Special Issue Glioblastoma)
Open AccessReview MicroRNA in Human Glioma
Cancers 2013, 5(4), 1306-1331; doi:10.3390/cancers5041306
Received: 22 September 2013 / Revised: 8 October 2013 / Accepted: 10 October 2013 / Published: 23 October 2013
Cited by 16 | PDF Full-text (540 KB) | HTML Full-text | XML Full-text
Abstract
Glioma represents a serious health problem worldwide. Despite advances in surgery, radiotherapy, chemotherapy, and targeting therapy, the disease remains one of the most lethal malignancies in humans, and new approaches to improvement of the efficacy of anti-glioma treatments are urgently needed. Thus, new
[...] Read more.
Glioma represents a serious health problem worldwide. Despite advances in surgery, radiotherapy, chemotherapy, and targeting therapy, the disease remains one of the most lethal malignancies in humans, and new approaches to improvement of the efficacy of anti-glioma treatments are urgently needed. Thus, new therapeutic targets and tools should be developed based on a better understanding of the molecular pathogenesis of glioma. In this context, microRNAs (miRNAs), a class of small, non-coding RNAs, play a pivotal role in the development of the malignant phenotype of glioma cells, including cell survival, proliferation, differentiation, tumor angiogenesis, and stem cell generation. This review will discuss the biological functions of miRNAs in human glioma and their implications in improving clinical diagnosis, prediction of prognosis, and anti-glioma therapy. Full article
(This article belongs to the Special Issue Glioblastoma)
Open AccessReview Is Glioblastoma an Epigenetic Malignancy?
Cancers 2013, 5(3), 1120-1139; doi:10.3390/cancers5031120
Received: 15 July 2013 / Revised: 13 August 2013 / Accepted: 19 August 2013 / Published: 3 September 2013
Cited by 12 | PDF Full-text (544 KB) | HTML Full-text | XML Full-text
Abstract
Epigenetic modifications control gene expression by regulating the access of nuclear proteins to their target DNA and have been implicated in both normal cell differentiation and oncogenic transformation. Epigenetic abnormalities can occur both as a cause and as a consequence of cancer. Oncogenic
[...] Read more.
Epigenetic modifications control gene expression by regulating the access of nuclear proteins to their target DNA and have been implicated in both normal cell differentiation and oncogenic transformation. Epigenetic abnormalities can occur both as a cause and as a consequence of cancer. Oncogenic transformation can deeply alter the epigenetic information enclosed in the pattern of DNA methylation or histone modifications. In addition, in some cancers epigenetic dysfunctions can drive oncogenic transformation. Growing evidence emphasizes the interplay between metabolic disturbances, epigenomic changes and cancer, i.e., mutations in the metabolic enzymes SDH, FH, and IDH may contribute to cancer development. Epigenetic-based mechanisms are reversible and the possibility of “resetting” the abnormal cancer epigenome by applying pharmacological or genetic strategies is an attractive, novel approach. Gliomas are incurable with all current therapeutic approaches and new strategies are urgently needed. Increasing evidence suggests the role of epigenetic events in development and/or progression of gliomas. In this review, we summarize current data on the occurrence and significance of mutations in the epigenetic and metabolic enzymes in pathobiology of gliomas. We discuss emerging therapies targeting specific epigenetic modifications or chromatin modifying enzymes either alone or in combination with other treatment regimens. Full article
(This article belongs to the Special Issue Glioblastoma)
Open AccessReview Emerging Biomarkers in Glioblastoma
Cancers 2013, 5(3), 1103-1119; doi:10.3390/cancers5031103
Received: 29 June 2013 / Revised: 14 August 2013 / Accepted: 19 August 2013 / Published: 22 August 2013
Cited by 20 | PDF Full-text (400 KB) | HTML Full-text | XML Full-text
Abstract
Glioblastoma, the most common primary brain tumor, has few available therapies providing significant improvement in survival. Molecular signatures associated with tumor aggressiveness as well as with disease progression and their relation to differences in signaling pathways implicated in gliomagenesis have recently been described.
[...] Read more.
Glioblastoma, the most common primary brain tumor, has few available therapies providing significant improvement in survival. Molecular signatures associated with tumor aggressiveness as well as with disease progression and their relation to differences in signaling pathways implicated in gliomagenesis have recently been described. A number of biomarkers which have potential in diagnosis, prognosis and prediction of response to therapy have been identified and along with imaging modalities could contribute to the clinical management of GBM. Molecular biomarkers including O(6)-methlyguanine-DNA-methyltransferase (MGMT) promoter and deoxyribonucleic acid (DNA) methylation, loss of heterozygosity (LOH) of chromosomes 1p and 19q, loss of heterozygosity 10q, isocitrate dehydrogenase (IDH) mutations, epidermal growth factor receptor (EGFR), epidermal growth factor, latrophilin, and 7 transmembrane domain-containing protein 1 on chromosome 1 (ELTD1), vascular endothelial growth factor (VEGF), tumor suppressor protein p53, phosphatase and tensin homolog (PTEN), p16INK4a gene, cytochrome c oxidase (CcO), phospholipid metabolites, telomerase messenger expression (hTERT messenger ribonucleic acid [mRNA]), microRNAs (miRNAs), cancer stem cell markers and imaging modalities as potential biomarkers are discussed. Inclusion of emerging biomarkers in prospective clinical trials is warranted in an effort for more effective personalized therapy in the future. Full article
(This article belongs to the Special Issue Glioblastoma)
Open AccessReview Formulations for Intranasal Delivery of Pharmacological Agents to Combat Brain Disease: A New Opportunity to Tackle GBM?
Cancers 2013, 5(3), 1020-1048; doi:10.3390/cancers5031020
Received: 29 June 2013 / Revised: 29 June 2013 / Accepted: 2 August 2013 / Published: 14 August 2013
Cited by 27 | PDF Full-text (508 KB) | HTML Full-text | XML Full-text
Abstract
Despite recent advances in tumor imaging and chemoradiotherapy, the median overall survival of patients diagnosed with glioblastoma multiforme does not exceed 15 months. Infiltration of glioma cells into the brain parenchyma, and the blood-brain barrier are important hurdles to further increase the efficacy
[...] Read more.
Despite recent advances in tumor imaging and chemoradiotherapy, the median overall survival of patients diagnosed with glioblastoma multiforme does not exceed 15 months. Infiltration of glioma cells into the brain parenchyma, and the blood-brain barrier are important hurdles to further increase the efficacy of classic therapeutic tools. Local administration methods of therapeutic agents, such as convection enhanced delivery and intracerebral injections, are often associated with adverse events. The intranasal pathway has been proposed as a non-invasive alternative route to deliver therapeutics to the brain. This route will bypass the blood-brain barrier and limit systemic side effects. Upon presentation at the nasal cavity, pharmacological agents reach the brain via the olfactory and trigeminal nerves. Recently, formulations have been developed to further enhance this nose-to-brain transport, mainly with the use of nanoparticles. In this review, the focus will be on formulations of pharmacological agents, which increase the nasal permeation of hydrophilic agents to the brain, improve delivery at a constant and slow release rate, protect therapeutics from degradation along the pathway, increase mucoadhesion, and facilitate overall nasal transport. A mounting body of evidence is accumulating that the underexplored intranasal delivery route might represent a major breakthrough to combat glioblastoma. Full article
(This article belongs to the Special Issue Glioblastoma)
Open AccessReview Glioblastoma-Initiating Cells: Relationship with Neural Stem Cells and the Micro-Environment
Cancers 2013, 5(3), 1049-1071; doi:10.3390/cancers5031049
Received: 26 June 2013 / Revised: 29 July 2013 / Accepted: 1 August 2013 / Published: 14 August 2013
Cited by 21 | PDF Full-text (3801 KB) | HTML Full-text | XML Full-text
Abstract
Glioblastoma multiforme (GBM, WHO grade IV) is the most common and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. The presence in GBM of a cancer population displaying neural stem cell (NSC)
[...] Read more.
Glioblastoma multiforme (GBM, WHO grade IV) is the most common and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. The presence in GBM of a cancer population displaying neural stem cell (NSC) properties as well as tumor-initiating abilities and resistance to current therapies suggests that these glioblastoma-initiating cells (GICs) play a central role in tumor development and are closely related to NSCs. However, it is nowadays still unclear whether GICs derive from NSCs, neural progenitor cells or differentiated cells such as astrocytes or oligodendrocytes. On the other hand, NSCs are located in specific regions of the adult brain called neurogenic niches that have been shown to control critical stem cell properties, to nourish NSCs and to support their self-renewal. This “seed-and-soil” relationship has also been adapted to cancer stem cell research as GICs also require a specific micro-environment to maintain their “stem cell” properties. In this review, we will discuss the controversies surrounding the origin and the identification of GBM stem cells and highlight the micro-environment impact on their biology. Full article
(This article belongs to the Special Issue Glioblastoma)

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