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Oncogene Apr 2012Glioblastoma is the most common and deadly of the primary central nervous system tumors. Recent advances in molecular characterization have subdivided these tumors into... (Review)
Review
Glioblastoma is the most common and deadly of the primary central nervous system tumors. Recent advances in molecular characterization have subdivided these tumors into at least three main groups. In addition, these tumors are cellularly complex with multiple stromal cell types contributing to the biology of the tumor and treatment response. Because essentially all glioma patients are treated with radiation, various chemotherapies and steroids, the tumor that finally kills them has been modified by these treatments. Most of the investigation of the effects of therapy on these tumors has focused on the glioma cells per se. However, despite the importance of the stromal cells in these tumors, little has been done to understand the effects of treatment on stromal cells and their contribution to disease. Understanding how current standard therapy affects the biology of the tumor and the tumor stroma may provide insight into the mechanisms that are important to the inhibition of tumor growth as well as the biology of recurrent tumors.
Topics: Brain Neoplasms; Glioma; Humans; Standard of Care; Stromal Cells
PubMed: 21909136
DOI: 10.1038/onc.2011.398 -
Journal of Neuro-oncology Oct 2003Human malignant glioma cell lines, primary cell cultures, and tumor specimens derived from surgical samples have been shown to overexpress high-affinity receptors (R)... (Review)
Review
Human malignant glioma cell lines, primary cell cultures, and tumor specimens derived from surgical samples have been shown to overexpress high-affinity receptors (R) for interleukin-4 (IL-4) in vitro and in situ. The significance of IL-4R expression on malignant glioma cells is still unclear. However, IL-4 has been reported to mediate functional effects in several solid tumor cell lines. These activities include inhibition of cell proliferation, regulation of adhesion molecules, and induction of signal transduction through the JAK/STAT pathway. To target IL-4Rs on tumor cells, we have produced a chimeric recombinant fusion protein consisting of a binding ligand, circularly permuted IL-4 and a mutated form of Pseudomonas exotoxin. This molecule is termed IL4(38-37)-PE38KDEL, cpIL4-PE, or IL-4 cytotoxin. Recombinant cpIL4-PE is highly and specifically cytotoxic to glioma cell lines in vitro, while it is not cytotoxic or less cytotoxic to hematopoietic and normal brain cells. In a nude mouse model, cpIL4-PE showed significant antitumor activity and partial or complete regression of small or large established human glioblastoma tumors. Encouraging preclinical efficacy, safety, and tolerability studies lead to testing of this agent in patients with recurrent glioblastoma. Based on these pilot studies, an extended Phase I/II clinical trial is currently ongoing to determine safety, tolerability, and efficacy of cpIL4-PE when injected stereotactically directly into the recurrent glioma by convection enhanced delivery. Preliminary clinical results suggest that cpIL4-PE can cause pronounced necrosis of recurrent glioma tumors without systemic toxicity. The central nervous system toxicities observed were attributed to the volume of infusion and/or nonspecific toxicity. Ongoing clinical trials will reveal antitumor activities of IL-4 cytotoxin in recurrent malignant glioma.
Topics: Animals; Brain Neoplasms; Clinical Trials as Topic; Drug Evaluation, Preclinical; Glioma; Humans; Immunotoxins; Interleukin-4; Receptors, Interleukin-4; Recombinant Fusion Proteins
PubMed: 14649882
DOI: 10.1023/a:1026294416718 -
Current Treatment Options in Oncology Feb 2008Adults with glioblastoma multiforme (GBM), the most common primary brain tumor, have an unacceptably poor outcome with conventional cytotoxic therapies. Malignant... (Review)
Review
Adults with glioblastoma multiforme (GBM), the most common primary brain tumor, have an unacceptably poor outcome with conventional cytotoxic therapies. Malignant gliomas are remarkably angiogenic, and vascular endothelial growth factor (VEGF) is the dominant pro-angiogenic factor. Recent clinical trials targeting VEGF signaling have achieved unprecedented rates of durable radiographic and clinical response, while also confirming adequate safety among recurrent malignant glioma patients. An array of additional clinical trials evaluating anti-angiogenic strategies are underway for both recurrent and newly diagnosed malignant glioma patients. Promising results of these approaches suggest that the treatment of GBM may represent an emerging paradigm of anti-angiogenic therapy.
Topics: Angiogenesis Inhibitors; Brain Neoplasms; Clinical Trials as Topic; Glioma; Humans; Vascular Endothelial Growth Factor A
PubMed: 18256938
DOI: 10.1007/s11864-008-0052-6 -
Brain and Nerve = Shinkei Kenkyu No... Mar 2007Despite advances in radiation and chemotherapy along with surgical resectioning, the prognosis of patients with malignant glioma is poor. Therefore, the development of a... (Review)
Review
Despite advances in radiation and chemotherapy along with surgical resectioning, the prognosis of patients with malignant glioma is poor. Therefore, the development of a new treatment modality is extremely important. There are increasing reports demonstrating that systemic immunotherapy using peptide is capable of inducing an antiglioma response. This review highlights peptide-based immunotherapy for glioma patients. Peptide-based immunotherapy strategies appear promising as an approach to successfully induce an antitumor immune response and increase survival in patients with glioma. Peptide-based therapy of glioma seems to be safe and without major side effects. Biotherapy for malignant glioma with peptide will open a novel reality now.
Topics: Animals; Antigens, Neoplasm; Brain Neoplasms; Cancer Vaccines; Central Nervous System; Glioma; Humans; Immunotherapy; Immunotherapy, Active; Vaccines, Subunit
PubMed: 17370651
DOI: No ID Found -
Neurologia Medico-chirurgica Jul 2017Positron emission tomography (PET) is being increasingly utilized for the management of brain tumors. Herein, we primarily review our previous studies on the use of PET... (Review)
Review
Positron emission tomography (PET) is being increasingly utilized for the management of brain tumors. Herein, we primarily review our previous studies on the use of PET in glioma that utilize three types of tracers: C-methionine (MET), C-choline, and F-fluorodeoxyglucose. These studies included aspects such as tumor behavior, diagnosis, grade of malignancy, spread and invasion, viability, and genetic deletions; moreover, they also evaluated PET as a tool for planning radiation therapy (RT) and determining its outcome. MET-PET in particular is considered to be the most informative for diagnosis and therapeutic decision-making for glioma patients; it is therefore considered crucial for brain tumor therapy. MET-PET is expected to be widely used for brain tumor patients going forward.
Topics: Central Nervous System Neoplasms; Glioma; Humans; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 28458384
DOI: 10.2176/nmc.ra.2016-0312 -
The Oncologist Feb 2006Treatment of malignant glioma requires a multidisciplinary team. Treatment includes surgery, radiotherapy, and chemotherapy. Recently developed agents have demonstrated... (Review)
Review
Treatment of malignant glioma requires a multidisciplinary team. Treatment includes surgery, radiotherapy, and chemotherapy. Recently developed agents have demonstrated activity against recurrent malignant glioma and efficacy if given concurrently with radiotherapy in the upfront setting. Oligodendroglioma with 1p/19q deletions has been recognized as a distinct pathologic entity with particular sensitivity to radiotherapy and chemotherapy. Randomized trials have shown that early neoadjuvant or adjuvant administration of procarbazine, lomustine, and vincristine chemotherapy prolongs disease-free survival; however, it has no impact on overall survival. Temozolomide, a novel alkylating agent, has shown modest activity against recurrent glioma. In combination with radiotherapy in newly diagnosed patients with glioblastoma, temozolomide significantly prolongs survival. Molecular studies have demonstrated that the benefit is mainly observed in patients whose tumors have a methylated methylguanine methyltransferase gene promoter and are thus unable to repair some of the chemotherapy-induced DNA damage. For lower-grade glioma, the use of chemotherapy remains limited to recurrent disease, and first-line administration is the subject of ongoing clinical trials. Irinotecan and agents like gefitinib, erlotinib, and imatinib targeting the epidermal growth factor receptor and platelet-derived growth factor receptor have shown some promise in recurrent malignant glioma. This review summarizes recent developments, focusing on the clinical management of patients in daily neuro-oncology practice.
Topics: Adult; Age Factors; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Glioma; Humans; Interprofessional Relations; Middle Aged; Patient Care Team; Prognosis; Randomized Controlled Trials as Topic
PubMed: 16476837
DOI: 10.1634/theoncologist.11-2-165 -
Expert Review of Neurotherapeutics Oct 2006Malignant gliomas are the most common type of primary brain tumor and are in great need of novel therapeutic approaches. Advances in treatment have been very modest,... (Review)
Review
Malignant gliomas are the most common type of primary brain tumor and are in great need of novel therapeutic approaches. Advances in treatment have been very modest, significant improvement in survival has been lacking for many decades and prognosis remains dismal. Despite 'gross total' surgical resections and currently available radio-chemotherapy, malignant gliomas inevitably recur due to reservoirs of notoriously invasive tumor cells that infiltrate adjacent and nonadjacent areas of normal brain parenchyma. In principle, the immune system is uniquely qualified to recognize and target these infiltrative pockets of tumor cells, which have generally eluded conventional treatment approaches. In the span of the last 10 years, our understanding of the cancer-immune system relationship has increased exponentially, and yet, we are only beginning to tease apart the intricacies of the CNS and immune cell interactions. This article reviews the complex associations of the immune system with brain tumors. We provide an overview of currently available treatment options for malignant gliomas, existing gaps in our knowledge of brain tumor immunology, and molecular techniques and targets that might be exploited for improved patient stratification and design of 'custom immunotherapeutics'. We will also examine major new immunotherapy approaches that are being actively investigated to treat patients with malignant glioma, and identify some current and future research priorities in this area.
Topics: Brain Neoplasms; Glioma; Humans; Immunization, Passive
PubMed: 17078788
DOI: 10.1586/14737175.6.10.1481 -
Progress in Lipid Research Oct 2013Malignant gliomas are the most common adult brain cancers. In spite of aggressive treatment, recurrence occurs in the great majority of patients and is invariably fatal.... (Review)
Review
Malignant gliomas are the most common adult brain cancers. In spite of aggressive treatment, recurrence occurs in the great majority of patients and is invariably fatal. Polyunsaturated fatty acids are abundant in brain, particularly ω-6 arachidonic acid (AA) and ω-3 docosahexaenoic acid (DHA). Although the levels of ω-6 and ω-3 polyunsaturated fatty acids are tightly regulated in brain, the ω-6:ω-3 ratio is dramatically increased in malignant glioma, suggesting deregulation of fundamental lipid homeostasis in brain tumor tissue. The migratory properties of malignant glioma cells can be modified by altering the ratio of AA:DHA in growth medium, with increased migration observed in AA-rich medium. This fatty acid-dependent effect on cell migration is dependent on expression of the brain fatty acid binding protein (FABP7) previously shown to bind DHA and AA. Increased levels of enzymes involved in eicosanoid production in FABP7-positive malignant glioma cells suggest that FABP7 is an important modulator of AA metabolism. We provide evidence that increased production of eicosanoids in FABP7-positive malignant glioma growing in an AA-rich environment contributes to tumor infiltration in the brain. We discuss pathways and molecules that may underlie FABP7/AA-mediated promotion of cell migration and FABP7/DHA-mediated inhibition of cell migration in malignant glioma.
Topics: Arachidonic Acid; Brain Neoplasms; Docosahexaenoic Acids; Fatty Acid-Binding Proteins; Fatty Acids, Unsaturated; Glioma; Humans; Prognosis
PubMed: 23981365
DOI: 10.1016/j.plipres.2013.08.004 -
Radiotherapy and Oncology : Journal of... Sep 2002A systematic review was conducted to develop guidelines for radiotherapy in adult patients with newly diagnosed malignant glioma. (Review)
Review
PURPOSE
A systematic review was conducted to develop guidelines for radiotherapy in adult patients with newly diagnosed malignant glioma.
METHODS
MEDLINE, CANCERLIT, the Cochrane Library, and relevant conference proceedings were searched to identify randomized trials and meta-analyses.
RESULTS
Pooling of six randomized trials detected a significant survival benefit favouring post-operative radiotherapy compared with no radiotherapy (risk ratio, 0.81; 95% confidence interval, 0.74 to 0.88, P<0.00001). Two randomized trials demonstrated no significant difference in survival rates for whole brain radiation versus more local fields that encompass the enhancing primary plus a 2 cm margin. A randomized trial detected a small improvement in survival with 60 Gy in 30 fractions over 45 Gy in 20 fractions. Radiation dose intensification and radiation sensitizer approaches have not demonstrated superior survival rates compared with conventionally fractionated doses of 50-60 Gy.
CONCLUSIONS
Post-operative external beam radiotherapy is recommended as standard therapy for patients with malignant glioma. The high-dose volume should incorporate the enhancing tumour plus a limited margin (e.g. 2 cm) for the planning target volume, and the total dose delivered should be in the range of 50-60 Gy in fraction sizes of 1.8-2.0 Gy. Radiation dose intensification and radiation sensitizer approaches are not recommended as standard care. For patients older than age 70, preliminary data suggest that the same survival benefit can be achieved with less morbidity using a shorter course of radiotherapy. Supportive care alone is a reasonable therapeutic option in patients older than age 70 with a poor performance status.
Topics: Adult; Brain Neoplasms; Chemotherapy, Adjuvant; Combined Modality Therapy; Dose Fractionation, Radiation; Dose-Response Relationship, Radiation; Glioma; Humans; Radiosurgery; Radiotherapy Dosage; Randomized Controlled Trials as Topic; Survival Rate
PubMed: 12242114
DOI: 10.1016/s0167-8140(02)00078-6 -
Annals of Oncology : Official Journal... Nov 1998Recent advances in molecular tumor biology and gene technology have provided the possibility to treat patients with malignant brain tumors by altering gene expression in... (Review)
Review
Recent advances in molecular tumor biology and gene technology have provided the possibility to treat patients with malignant brain tumors by altering gene expression in tumor cells. Tumor development and progression involves alterations in a wide spectrum of genes, therefore a variety of gene therapy approaches for malignant gliomas have been proposed. In this review article, we discuss some principles of current gene therapeutic strategies that are under investigation in laboratories and in clinics. In addition, some general issues that remain to be resolved for clinical application of gene therapy in patients with malignant gliomas will be addressed.
Topics: Animals; Brain Neoplasms; Clinical Trials as Topic; Genetic Therapy; Glioma; Humans
PubMed: 9862044
DOI: 10.1023/a:1008488709359