| Neuro-oncology DTI |
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| Diffusion Tensor Imaging of white matter tracts relative to tumor |
Neuro-oncology is the study of neoplasms associated with the central and peripheral nervous system. While the diseases which fall under the purview of neuro-oncology only account for 2.4% of all cancer deaths, these illnesses are often extremely malignant with only 33.5% of patients diagnosed with a neuro-oncological cancer surviving for 5 years. By mainly restricting our study to one type of brain cancer: glioma, it is possible to address a number of topics such as causes, diagnosis, and treatments of glial-based cancers. Malignant gliomas account for approximately 70% of all new primary brain tumour cases in the U.S each year [1].
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Table of Contents |
Clinical Presentation and Molecular Diagnosis of Glioma
main article: Clinical Presentation and Molecular Diagnosis of Glioma
author: 
(account deleted)
| Figure 1. Glioblastoma multiforme (GBM) shown on an MRI scan. |
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| Mass found in the left side of the image represents a GBM lesion. Adapted from “Fighting Cancer with Cancer”. Retrieved from URL: http://blogs.lt.vt.edu/jennasack/2013/03/27/fighting-cancer-with-cancer/ |
Brain tumours are neoplasms that primarily arise from cells of the brain parenchyma. Brain tumours that arise from glial cells, or gliomas, account for more than 70% of all brain tumours in humans, with glioblastoma multiforme (GBM) being the most common (Figure 1). GBM is a neoplasm that arises from astrocytes, though all glial cell types may give rise to a glioma [1-2]. Population studies have indicated GBM is also the most malignant brain tumour, with a less than 3% 5 year survival rate [3]. Gliomas can be either primary (de novo) or secondary. Primary gliomas arise from mutations in normal glial cells that lead to oncogenesis of the cell, and show no evidence of having arose from a less malignant precursor lesion or neoplasm. Secondary gliomas can arise from lower grade (discussed below) non-malignant tumours already present and acquire malignant characteristics [4]. Gliomas can be diagnosed mainly by radiology or histology. In general, histological classification is the best way to currently diagnose a glioma [5]. Most symptoms upon physical examination do not specifically identify any type of glioma (or any CNS neoplasm for that matter), making it difficult to diagnose a patient based on physical examination alone. Physical symptoms however depend on different factors such as the location of the tumour and age of those affected. Newer molecular methods could potentially be used to distinguish glioma subtypes, predict patient outcome and provide mechanistic insight into the pathology of the disease.
Dietary Factors in Neurooncology
main article: Dietary Factors in Neurooncology
author: Rebecca Fritz
| Anti-Cancer Diet |
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| courtesy of http://listcrown.com/wp-content/uploads/2013/09/protect-against-certain-types-of-cancers.jpg |
Diet is a major environmental factor that can play a role in initial development, prevention, and progression of malignant brain tumours in both positive and negative ways. Although there are no components of the diet that are proven to be direct causes of brain tumours, certain components are consistently shown to be correlated with a higher incidence of brain cancer, while others are linked to a lower risk or are suggested to slow the progression of the tumour. N-nitroso compounds are elevated in diets higher in nitrites, and are suspected to have neurocarcinogenic effects. Anti-oxidative properties of vitamins and other nutrients are thought to antagonize the effect that these nitroso compounds have, thereby reducing risk of developing brain cancer[1]. Both an individuals diet and maternal diet during pregnancy are thought to play a role. Diet can also be used as a method for treatment by using certain diets to induce metabolic alterations, intending to restrict energy sources from the tumour cells. New methods to manage brain tumours are critical because of their aggressive nature and limited effective and safe treatment options. At present, the ketogenic diet is a promising option for management of brain tumours, working to slow their growth[[2]].
Fundametal Genetics of Glioblastoma Multiforme
main article: Fundametal Genetics of Glioblastoma Multiforme
author: Kevin Grykuliak
| Genetic Etiologies of Glioblastoma Multiforme |
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| Recent studies in genetic sequencing have found strong causal links between the presentation of select genes and the presentation of glioblastoma multiforme in mice and humans. Some examples of genes that appear to have a strong influence on the expression of GBM are illustrated here. Picture from http://newsroom.cumc.columbia.edu/[3] |
The importance of understanding the causal factors of gliomas cannot be understated: malignant gliomas account for approximately 70% of all new primary brain tumor cases in the U.S. each year. However, the definition of cancer as an expressed phenotype implies that there must be an interaction between genetic and environmental factors in order for expression of this disease to occur. Since the causes of most cancers are extremely complex, it is necessary to restrict the scope of causal research to primarily genetic causes of one specific type of cancer. An analysis of genetic etiologies for glioblastoma multiforme (GBM) – a specific type of glioma – serves as an effective paradigm for many types of gliomas and has a considerable amount of research available for discussion.
An effective way to discuss genetic pathways responsible for GBM is to classify them according to the number of genes required to create the cancerous phenotype. Some genetic mutations are extremely localized: fusion of two wild-type genes (FGFR and TACC) is sufficient to have a statistically significant effect on the development of GBM: approximately 3.1% of all GBM patients express this genetic defect.[1] On the other hand, for some large gene pathways, oncogenic effects may require multiple defects in order for the development of GBM to occur (often due to the effectiveness of tumor suppressors and other protective mechanisms). Multiple mutations in developmental pathways for particular types of glial cells, including the PDGF/PDGFR pathway, can cause the cells to regress into an earlier (cancerous) form and migrate throughout the body.[2] Therefore, due to the varying “strength” of a specific oncogene, it is extremely important to understand how the effects of an oncogene, or set of oncogenes, can be quantified before an attempt at developing genetic treatments can occur. However, due to the vast array of genetic variations and separate causes of GBM that occur, it will be necessary to restrict the specific examples of single-gene and multi-gene pathways to one paradigm pathway for each category.
Immunotherapy for Glioblastoma
main article: Immunotherapy for Glioblastoma
author: Hang Diep
| Vaccine Against Brain Cancer |
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| Picture from http://www.columbianeurosurgery.org/ |
Glioblastoma multiforme (GBM) is a lethal disease that has no known cure with the median survival of less than 15 months [1]. Common treatments such as surgery, radiotherapy, and chemotherapy are not much effective in treating glioblastomas. Immunotherapy is a promising approach to treatment of glioblastoma multiforme as it targets only the tumour cells while leaving other healthy cells alone. Tumour resistance has been associated with angiogenesis, immune suppression of cytokines, B cells and T cells, as well as other reduced immune responses. Based on these aspects, different immuno-therapeutic approaches have been studied and showed promising results such as angiogenic inhibitors, vaccine therapy, and cell-based therapy [1]. In fact, the first cell-based therapy was authorized to be used in treating prostate cancer in 2011 [1], promoting new immunotherapeutic approaches for treatment of cancer. Currently, some immunotherapies have shown some promising results for treatment of GBM. Some potential examples are peptide-based vaccines, dendritic cell (DC) vaccines, and induced adoptive immunity. These studies are currently in phase III clinical trial.
MicroRNA Biomarkers in Glioblastoma
main article: MicroRNA Biomarkers in Glioblastoma
author: Reem Helmy
| MicroRNA Biomarker |
| Picture from http://www.nyas.org/publications/EBriefings/Detail.aspx? cid=8fbe52e3-c4d3-4c44-bed5-1d5d2fcc81c3 |
MicroRNAs are excellent plasma biomarker candidates in cancer, as they are usually deregulated in glioblastomas. Compared to other blood biomarkers, such as mRNA, MicroRNAs have demonstrated to be the most reliable. The concentration of these blood biomarkers yields many factors that are associated with tumor activity. MicroRNAs regulate gene expression and can enhance or supress translational processes. Similar to oncogenes, “oncomirs” (MicroRNAs that have enhanced expression in cancer), can suppress the tumor suppressor genes in the surrounding genome[1]. Similarly, some Micro-RNAs can also function as tumor suppressors or effect methylation. Glioblastomas are the most common and malignant type of brain tumor found amongst adults. As a result, many Profiling techniques have been identified and implemented on distinct microRNA expression patterns in glioblastomas. Among these techniques are microarray, qRT-PCR, In situ hybridization, and RNA sequencing, each applying to a specific line of Micro-RNAs. Some have shown more advantageous in the quantity of samples, while others provide enhanced quality, encouraging further detection of biomarkers and tumors [2]. Currently, there are more than 1,400 microRNA sequences listed from studies, but much has yet to be clarified on their accuracy and precision, for their use as an early diagnostic method and perhaps a therapeutic approach.
Molecular and Protein Pathways in Glioblastoma Multiforme
main article: Molecular and Protein Pathways in Glioblastoma Multiforme
author: Arsalan Mir
| Cancer Glioblastoma |
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| Different factors contribute to the formation of glioblastoma multiforme, these include cell proliferation, de-differentiation, invasiveness and motility |
Glioblastoma multiforme (GBM) is the most aggressive and malignant type of brain tumor that has a very short survival rate.[1] The cells involved in producing the Glioblastoma are involved in either one or multiple gene mutations that have compromised the normal cellular function of glia cells. Therefore, the cancer shares in common similar characteristics of other tumors such as excessive, motility, invasiveness, proliferation, and differentiation that are brought about by the specific mutation of some genes. Although there are many proteins that induce the cancer, different proteins either individually or cooperatively produce the Glioblastoma multiforme cancer, which points to the delicate balance of expressed proteins and how simply the balance can be compromised. In addition, to single protein mutations that may result in cancer, viruses such as Human papillomavirus are also involved in oncoprotein pathways that lead to gliomas. [2] Therefore, viruses or other environmental agents may also lead to the over expression or down regulation of essential proteins, which can have detrimental effects. Here, we investigate the different proteins that may lead to the progression of cancer and different the environmental causes such as viruses and carcinogenic agents that compromise the normal functioning of the proteins and later lead to tumor formation.
Glioblastoma multiforme presents in different sub-types with unique genetic and protein expressions. The four sub-types for the primary GBM include Classical, Proneural, Mesenchymal, and Neural. [2] Within each of the subtypes, there are characteristic genes or proteins that become mutated or overexpressed which lead to tumors.
Nanotechnology in Glioblastoma Multiforme
main article: Nanotechnology in Glioblastoma Multiforme
author: Mikaela Manley
| Nanotechnology in the CNS |
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| Courtesy of Azonano.com |
Neurooncology, or the study of cancer within the nervous system, is a field in which there is new and constant research being published to help improve both diagnostic tools and treatments. Nanotechnology is one of these such new techniques and it has recently began to be used in both areas, specifically with recurrent glioblastoma multiforme, a type of cancer within the central nervous system. Thus far, there are very limited or effective treatments for GM within the CNS and an earlier diagnosis has proven to be difficult, however improvements in diagnosis and treatment are possible with the introduction of nanoparticles.
Nanoparticles are structures 1-100nm in size with new and/or enhanced properties compared to the original quantum and molecular structure of the compound and are encased by either a monosaccharide or polysaccharide[1]. They have a wind range of use including improving magnetic resonance imaging contrast and passing the blood brain barrier to either directly stimulate and denature tumors or provide transport and protection for an anti-cancer drug[2].
Neural Stem Cell-based Gene Therapy
main article: Neural Stem Cell-based Gene Therapy
author: TansyZ
| Gene therapy comes of age: edit genomes to cure diseases |
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| Retrieved from:Web: ExtremeTech |
Malignant brain tumors can be grouped into two categories base on its cell origin. Primary brain tumors arise from the various cells that make up the brain and central nervous system while secondary brain tumors results from metastasis of other malignancy outside of nerve system. Glioma and astrocytoma are two most common types of primary malicious brain tumors. Patients diagnosed with malignant brain tumor in general have poor prognosis. For example,Glioblastoma multiforme (GBM), the most common and lethal type of adult primary brain tumors, have a median survival of less than 11 months.[1] Current stand of care for metastasis neoplasm is surgical resection followed by radiation and chemotherapy.[2] High remission of tumor growth and inevitable death despite extensive use of standard therapeutic interventions sets the demand for new treatment.
Gene therapy offers the promises of argumenting traditional cancer regimes as well as enabling new approaches. Therapeutic genes can act as cytotoxic agent, angiogenesis antagonist, immune response stimulator or restore endogenous anti-tumor regulation by supplementing the mutated genes that underlying certain cancer types.[3] However, the therapeutic effect of gene therapy is hindered by the inefficient delivery to site of action. Neural stem cells kick in as a powerful delivery vehicle thanks to their remarkable migratory and tumor- tropic properties.[4]
Neuroimaging Techniques in the Diagnosis of Glioma
main article: Neuroimaging Techniques in the Diagnosis of Glioma
author: Majid Gasim
| The functioning of an MRI machine |
| This video gives a brief description of the physics of an MRI machine. It describes the phenomenon of nuclear magnetic resonance, and how it's manipulated to produce 3D images. Video from:https://www.youtube.com/watch?v=pGcZvSG805Y [Bibliography item Video not found.] |
Neuroimaging techniques are one of the most important diagnostic tools used by physicians for the clinical assessment of brain tumors. They are usually integral to the initial evaluation and assessment of brain tumors in patients, and with modern advances in technology, they can sometimes provide a non-‐invasive method of diagnosis. Advanced methods of Magnetic resonance spectroscopy have also been shown to be able to differentiate between various forms of glioma subtypes, which could further aid diagnosis [1]. Furthermore, certain studies have demonstrated novel or advanced imaging techniques which allow for much improved delineation of Glioma margins, a useful tool for treatment evaluation and surgical guidance [2] . Hence, the importance of developing new, or modifying existing neuroimaging techniques cannot be understated.
Proton Beam Radiotherapy
main article: Proton Beam Radiotherapy
author: Nouran Sakr
| Proton Beam Radiotherapy |
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| A proton beam radiation device used in treatment. Retrieved from: orlandohealthdocs.com/ufhealthcancercenterorlando |
When treating malignant tumours that are associated with the nervous system, the use of radiation techniques such as photon intensity modulated radiation therapy (IMRT), which includes x-rays and gamma radiation, poses a great challenge. The spreading of the dose of radiation into the healthy structures surrounding the tumour often leads to cognitive deficits and the potential development of secondary brain tumours. Consequently, the use of proton radiotherapy as opposed to the conventional photon IMRT offers a considerably safer treatment approach when dealing with such malignancies. The proton’s properties allow for the specific targeting of the tumour tissue, while at the same time delivering a high enough dose of radiation, leading to the death of tumour cells. Hence, this achieves the optimal goal of eliminating the cancer tissue without causing collateral damage to the critical brain areas that are in close proximity to it. As a result, clinicians have been particularly using proton radiation to treat a wide range of pediatric brain tumours. Clinical research thus far has used proton beam radiation in the treatment of numerous brain malignancies including astrocytomas, medulloblastomas, oligodendrogliomas, optic nerve gliomas, acoustic neuromas, and many others types of tumours [1]. Unfortunately, clinical research appears to be somewhat limited. Moreover, much remains unclear about the precise mechanisms and biophysical properties of proton beams and further investigations in that area are critical. Recent research has been developing methods to further improve the dose distribution of proton radiation, which would pave way for an even higher cell death count in the tumour tissue and further sparing of the healthy tissue [2].