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Annals of Oncology : Official Journal... Jun 1998Despite more than two decades of clinical research with chemotherapy, the outcome of malignant gliomas remains poor. Recent years have seen major advances in elucidation... (Review)
Review
Despite more than two decades of clinical research with chemotherapy, the outcome of malignant gliomas remains poor. Recent years have seen major advances in elucidation of the biology of these tumors, which in turn have led to the current development of innovative therapeutic strategies. The question confronting us at the end of the 1990s is whether we should continue to use and investigate chemotherapy or whether the time has come for experimental treatments. As a contribution to this debate, we reviewed the abundant literature on chemotherapy of malignant glioma, paying special attention to methodological features. The new treatment approaches based on current knowledge about glioma biology are then briefly summarized. Assessment of more than 20 years of chemotherapy trials is discouraging despite a few areas of modest success. Only patients with specific histology (oligodendroglioma, anaplastic astrocytoma) and good prognostic factors (young age, good performance status) may benefit from chemotherapy, with a possible reversal of neurological dysfunction. However, the real impact on survival is small (anaplastic astrocytoma) or undefined (oligodendroglioma). Furthermore, it is unfortunately obvious that the outcome of glioblastoma patients is not significantly modified by chemotherapy. We believe the time has come to explore the potential of novel biological therapies in glioblastoma patients. This could also be proposed for anaplastic astrocytoma and oligodendroglioma patients after failure of chemotherapy.
Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Clinical Trials as Topic; Genetic Therapy; Glioma; Humans; Immunotherapy; Prognosis
PubMed: 9681071
DOI: 10.1023/a:1008267312782 -
Neurosurgery Oct 2011Despite advances in surgery, radiation, and chemotherapy, malignant gliomas are still highly lethal tumors. Traditional treatments that rely on nonspecific, cytotoxic... (Review)
Review
Despite advances in surgery, radiation, and chemotherapy, malignant gliomas are still highly lethal tumors. Traditional treatments that rely on nonspecific, cytotoxic approaches have a marginal impact on patient survival. However, recent advances in the molecular cancer biology underlying glioma pathogenesis have revealed that abnormalities in common cell surface receptors, including receptor tyrosine kinase and other cytokines, mediate the abnormal cellular signal pathways and aggressive biological behavior among the majority of these tumors. Some cell surface receptors have been targeted by novel agents in preclinical and clinical development. Such cancer-specific targeted agents might offer the promise of improved cancer control without substantial toxicity. Here, we review these common cell surface receptors with clinical significance for malignant glioma and discuss the molecular characteristics, pathological significance, and potential therapeutic application of these cell surface receptors. We also summarize the clinical trials of drugs targeting these cell surface receptors in malignant glioma patients.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Clinical Trials as Topic; Drug Delivery Systems; Glioma; Humans; Receptors, Cell Surface
PubMed: 21522029
DOI: 10.1227/NEU.0b013e318220a672 -
Acta Biochimica Et Biophysica Sinica May 2009Malignant gliomas represent the majority of primary brain tumors. The current standard treatments for malignant gliomas include surgical resection, radiation therapy,... (Review)
Review
Malignant gliomas represent the majority of primary brain tumors. The current standard treatments for malignant gliomas include surgical resection, radiation therapy, and chemotherapy. Radiotherapy, a standard adjuvant therapy, confers some survival advantages, but resistance of the glioma cells to the efficacy of radiation limits the success of the treatment. The mechanisms underlying glioma cell radioresistance have remained elusive. Autophagy is a protein degradation system characterized by a prominent formation of double-membrane vesicles in the cytoplasm. Recent studies suggest that autophagy may be important in the regulation of cancer development and progression and in determining the response of tumor cells to anticancer therapy. Also, autophagy is a novel response of glioma cells to ionizing radiation. Autophagic cell death is considered programmed cell death type II, whereas apoptosis is programmed cell death type I. These two types of cell death are predominantly distinctive, but many studies demonstrate a cross-talk between them. Whether autophagy in cancer cells causes death or protects cells is controversial. The regulatory pathways of autophagy share several molecules. PI3K/Akt/mTOR, DNA-PK, tumor suppressor genes, mitochondrial damage, and lysosome may play important roles in radiation-induced autophagy in glioma cells. Recently, a highly tumorigenic glioma tumor subpopulation, termed cancer stem cell or tumor-initiating cell, has been shown to promote therapeutic resistance. This review summarizes the main mediators associated with radiation-induced autophagy in malignant glioma cells and discusses the implications of the cancer stem cell hypothesis for the development of future therapies for brain tumors.
Topics: Autophagy; Brain Neoplasms; Cell Survival; Glioma; Humans; Models, Biological; Signal Transduction
PubMed: 19430698
DOI: 10.1093/abbs/gmp028 -
Current Treatment Options in Oncology Dec 2004Patients with local recurrent malignant gliomas present diagnostic and therapeutic challenges for the neuro-oncology practitioner. Management must be individualized... (Review)
Review
Patients with local recurrent malignant gliomas present diagnostic and therapeutic challenges for the neuro-oncology practitioner. Management must be individualized depending on the patient's age, performance status, histology, response to initial therapy, type of recurrence (local vs diffuse), and time since original diagnosis. Treatment options may be classified into surgery, additional radiation therapy, or chemotherapy. Results of treatment are often difficult to determine because of limitations of conventional imaging. Symptom palliation is an important goal that often requires additional adjuvant medical therapy. Quality of life issues are also of paramount importance in patients with recurrent malignant glioma and frequently will guide management strategy. Finally, patients with recurrent malignant gliomas should be encouraged to consider participation in a clinical trial in the hopes that better treatment alternatives will be available for this group of patients within the next few years.
Topics: Central Nervous System Neoplasms; Combined Modality Therapy; Glioma; Humans; Neoplasm Recurrence, Local; Quality of Life; Treatment Outcome
PubMed: 15509482
DOI: 10.1007/s11864-004-0037-z -
Clinical Neurosurgery 1968
Review
Topics: Antibodies; Antigens; Astrocytoma; Autoradiography; Blood-Brain Barrier; Brain; Brain Neoplasms; Ependymoma; Glioblastoma; Glioma; Humans; Immunization, Passive; Immunoglobulins; Iodine Isotopes; Neoplasm Recurrence, Local; Radionuclide Imaging
PubMed: 4333303
DOI: 10.1093/neurosurgery/15.cn_suppl_1.175 -
Expert Opinion on Drug Delivery Jun 2014Malignant gliomas remain one of medicine's most daunting unsolved clinical problems. The development of new technologies is urgently needed to improve the poor prognosis... (Review)
Review
INTRODUCTION
Malignant gliomas remain one of medicine's most daunting unsolved clinical problems. The development of new technologies is urgently needed to improve the poor prognosis of patients suffering from these brain tumors. Magnetic nanomaterials are appealing due to unique properties that allow for noninvasive brain tumor diagnostics and therapeutics in one multifunctional platform.
AREAS COVERED
We report on the recent advances of magnetic nanomaterials for brain tumor imaging and therapy, with an emphasis on novel approaches and clinical progress. We detail their biomedical applications including brain tumor targeting, MRI contrast enhancement, optical imaging, magnetic hyperthermia, magnetomechanical destruction, drug delivery, gene therapy, as well as tracking of cell-based and viral-based therapies. The clinical cases and obstacles encountered in the use of magnetic nanomaterials for malignant glioma are also examined.
EXPERT OPINION
To accelerate the effective translation of these materials to the clinic as theranostics for brain tumors, limitations such as poor intratumoral distribution, targeting efficiency and nonspecific systemic side effects must be addressed. Future innovations should focus on optimizing and combining the unique therapeutic applications of these magnetic nanomaterials as well as improving the selectivity of the system based on the molecular profiling of tumors.
Topics: Brain Neoplasms; Drug Delivery Systems; Genetic Therapy; Glioma; Humans; Magnetic Resonance Imaging; Magnetite Nanoparticles; Nanostructures
PubMed: 24766329
DOI: 10.1517/17425247.2014.912629 -
Onkologie Sep 2008
Topics: Antineoplastic Agents; Brain Neoplasms; Glioma; Humans; Neoadjuvant Therapy; Paclitaxel; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 18787348
DOI: 10.1159/000146065 -
Molecular Therapy : the Journal of the... Oct 2005Glioblastoma is an aggressive brain tumor with a dismal prognosis. Gene therapy may offer a new option for the treatment of these patients. Several gene therapy... (Review)
Review
Glioblastoma is an aggressive brain tumor with a dismal prognosis. Gene therapy may offer a new option for the treatment of these patients. Several gene therapy approaches have shown anti-tumor efficiency in experimental studies, and the first clinical trials for the treatment of malignant glioma were conducted in the 1990s. HSV-tk gene therapy has been the pioneering and most commonly used approach, but oncolytic conditionally replicating adenoviruses and herpes simplex virus mutant vectors, p53, interleukins, interferons, and antisense oligonucleotides have also been used. During the past few years, adenoviruses have become the most popular gene transfer vectors, and some recent randomized, controlled trials have shown significant anti-tumor efficacy in clinical use. However, efficient gene delivery into the brain still presents a major problem, and there is a lack of definitive phase III trials, which would avoid potential problems associated with a small number of patients, inadvertent patient selection, and overinterpretation of results based on a few long-time survivors. For clinical efficacy, median survival is one of the most rigorous endpoints. It is used here to evaluate the usefulness of various treatment approaches and current clinical status of gene therapy for malignant glioma.
Topics: Adenoviridae; Clinical Trials as Topic; Combined Modality Therapy; Genetic Therapy; Genetic Vectors; Glioma; Humans; Immunotherapy; Oligonucleotides, Antisense; Oncolytic Virotherapy
PubMed: 16095972
DOI: 10.1016/j.ymthe.2005.07.357 -
Brain Research. Brain Research Reviews Sep 1995Human malignant gliomas are rather resistant to all current therapeutic approaches including surgery, radiotherapy and chemotherapy as well as antibody-guided or... (Review)
Review
Human malignant gliomas are rather resistant to all current therapeutic approaches including surgery, radiotherapy and chemotherapy as well as antibody-guided or cellular immunotherapy. The immunotherapy of malignant glioma has attracted interest because of the immunosuppressed state of malignant glioma patients which resides mainly in the T-cell compartment. This T-cell suppression has been attributed to the release by the glioma cells of immunosuppressive factors like transforming growth factor-beta (TGF-beta) and prostaglandins. TGF-beta has multiple effects in the immune system, most of which are inhibitory. TGF-beta appears to control downstream elements of various cellular activation cascades and regulates the expression of genes that are essential for cell cycle progression and mitosis. Since TGF-beta-mediated growth arrest of T-cell lines results in their apoptosis in vitro, glioma-derived TGF-beta may prevent immune-mediated glioma cell elimination by inducing apoptosis of tumor-infiltrating lymphocytes in vivo. T-cell apoptosis in the brain may be augmented by the absence of professional antigen-presenting cells and of appropriate costimulating signals. Numerous in vitro studies predict that tumor-derived TGF-beta will incapacitate in vitro-expanded and locally administered lymphokine-activated killer cells (LAK-cells) or tumor-infiltrating lymphocytes. Thus, TGF-beta may be partly responsible for the failure of current adoptive cellular immunotherapy of malignant glioma. Recent experimental in vivo studies on non-glial tumors have corroborated that neutralization of tumor-derived TGF-beta activity may facilitate immune-mediated tumor rejection. Current efforts to improve the efficacy of immunotherapy for malignant glioma include various strategies to enhance the immunogenicity of glioma cells and the cytotoxic activity of immune effector cells, e.g., by cytokine gene transfer. Future strategies of cellular immunotherapy for malignant glioma will have to focus on rendering glioma cell-targeting immune cells resistent to local inactivation and apoptosis which may be induced by TGF-beta and other immunosuppressive molecules at the site of neoplastic growth. Cytotoxic effectors targeting Fas/APO-1, the receptor protein for perforin-independent cytotoxic T-cell killing, might be promising, since Fas/APO-1 is expressed by glioma cells but not by untransformed brain cells, and since Fas/APO-1-mediated killing in vitro is not inhibited by TGF-beta.
Topics: Apoptosis; Brain; Glioma; Humans; Immunotherapy; T-Lymphocytes; Transforming Growth Factor beta; Treatment Failure
PubMed: 8866671
DOI: 10.1016/0165-0173(95)00010-0 -
Advanced Healthcare Materials Dec 2023Resident microglia are key factors in mediating immunity against brain tumors, but the microglia in malignant glioma are functionally impaired. Little immunotherapy is...
Resident microglia are key factors in mediating immunity against brain tumors, but the microglia in malignant glioma are functionally impaired. Little immunotherapy is explored to restore microglial function against glioma. Herein, oleanolic acid (OA) (microglia "restorer") and PPA-1 peptide (immune checkpoint blockade) are integrated on a nano-immuno-synergist ( PAM@OA) to work coordinately. The self-assembled OA core is coated with macrophage membrane for efficient blood-brain barrier penetration and microglia targeting, on which PPA-1 peptide is attached via acid-sensitive bonds for specific release in tumor microenvironment. With the enhanced accumulation of the dual drugs in their respective action sites, PAM@OA effectively promotes the recruitment and activation of effector T cells by inhibiting aberrant activation of Signal transducer and activator of transcription (STAT-3) pathway in microglia, and assists activated effector T cells in killing tumor cells by blocking elevated immune checkpoint proteins in malignant glioma. Eventually, as adjuvant therapy, the rationally designed nano-immuno-synergist hinders malignant glioma progression and recurrence with or without temozolomide. The work demonstrates the feasibility of a nano-formulation for microglia-based immunotherapy, which may provide a new direction for the treatment of brain tumors.
Topics: Humans; Microglia; Glioma; Brain Neoplasms; Macrophages; Peptides; Tumor Microenvironment
PubMed: 37573475
DOI: 10.1002/adhm.202301861