Differences
This shows you the differences between two versions of the page.
| Both sides previous revision Previous revision Next revision | Previous revision | ||
|
group_2_presentation_1_-_glioblastoma [2017/10/06 19:54] morgal |
group_2_presentation_1_-_glioblastoma [2018/01/25 15:19] (current) |
||
|---|---|---|---|
| Line 1: | Line 1: | ||
| + | Link to ppt: https://docs.google.com/a/mcmaster.ca/presentation/d/1aPDGB9N-jfVw91J4yq4N44fnEg5pGluNftePloslFag/edit?usp=sharing | ||
| ====== Introduction ====== | ====== Introduction ====== | ||
| - | |||
| - | ===== Etiology ===== | ||
| Glioblastomas (GBM) are the most common aggressive malignant tumors found in adults (Davis 2016). The onset tends to occur in glial tissue of the central nervous system, with most tumors found in the brain. Primary glioblastomas originate de novo, meaning they do not arise from previously present tumors or cancerous precursors in the central nervous system. In contrast, secondary tumors arise from previously existing low grade tumors that develop into GBM (Davis, 2016). Most cases of GBM tend to be sporadic and result from a complex mutation rather than a genetic predisposition. However, the cancer can result from the metastasis of peripheral cancer cells located commonly in the breast and lungs, effectively evading immunological responses upon penetrating the blood-brain barrier (Davis, 2016) Moreover, Gliomas could be astrocytic, oligodendrocytic, or a mix of both. Overall, there are few potential carcinogenic risk factors that can influence the onset of glioblastoma in the central nervous system. For instance, exposure to high doses of ionizing radiation is regarded as the only confirmed risk factor (Davis, 2016). | Glioblastomas (GBM) are the most common aggressive malignant tumors found in adults (Davis 2016). The onset tends to occur in glial tissue of the central nervous system, with most tumors found in the brain. Primary glioblastomas originate de novo, meaning they do not arise from previously present tumors or cancerous precursors in the central nervous system. In contrast, secondary tumors arise from previously existing low grade tumors that develop into GBM (Davis, 2016). Most cases of GBM tend to be sporadic and result from a complex mutation rather than a genetic predisposition. However, the cancer can result from the metastasis of peripheral cancer cells located commonly in the breast and lungs, effectively evading immunological responses upon penetrating the blood-brain barrier (Davis, 2016) Moreover, Gliomas could be astrocytic, oligodendrocytic, or a mix of both. Overall, there are few potential carcinogenic risk factors that can influence the onset of glioblastoma in the central nervous system. For instance, exposure to high doses of ionizing radiation is regarded as the only confirmed risk factor (Davis, 2016). | ||
| Line 114: | Line 113: | ||
| === Genetic Instability === | === Genetic Instability === | ||
| - | Normal cells have tight regulations during the cell cycle to prevent mutations from occuring. However, when this tight regulation of the cell cycle is lost there will be an accumulation of genomic mutations during a series of cell divisions. These alterations will transform normal cells into precancerous cells. These cells would not be classified or diagnosed as cancer cells, however, these cells have a higher potential to be cancerous. The adition of more mutations that lead to increased growth trasform these cells into cancerous cells, and thus can be diagnsed as cancer. Furthermore, the cancer cells will continue to alter these cancer cells to be more malignant. Thus, genetic instability not only leads to tumorigenesis, but maintains the survivability of these cancer cells (Shen. 2011) | + | Normal cells have tight regulations during the cell cycle to prevent mutations from occuring. However, when this tight regulation of the cell cycle is lost there will be an accumulation of genomic mutations during a series of cell divisions. These alterations will transform normal cells into precancerous cells. These cells would not be classified or diagnosed as cancer cells, however, these cells have a higher potential to be cancerous. The addition of more mutations that lead to increased growth transform these cells into cancerous cells, and thus can be diagnosed as cancer. Furthermore, the cancer cells will continue to alter these cancer cells to be more malignant. Thus, genetic instability not only leads to tumorigenesis, but maintains the survivability of these cancer cells (Shen. 2011). The progression of normal cells to cancerous cells is outlined in figure 11. |
| {{ :gene_insta.png |}} | {{ :gene_insta.png |}} | ||
| Line 129: | Line 128: | ||
| **Bevacizumab (Avastin®)** | **Bevacizumab (Avastin®)** | ||
| - | Bevacizumab (Avastin®) is a monoclonal antibody implemented in GBM chemotherapeutic regiments to target vascular endothelial growth factor (VEGF) and was approved by the FDA in 2009 after clinical trials had demonstrated excellent performance. The VEGF protein is needed for angiogenesis, a process that involves the synthesis of new vasculature from pre-existing vessels and occurs during wound healing and when cells are deficient in oxygen levels. The synthesis of new blood vessels among tumor cells mediated by VEGF leads to a greater blood and oxygen supply necessary for the proliferation of GBM cells (Gil-Gil et al. 2013). Avastin works to reduce vascular permeability and edema, enhancing delivery of oxygen to brain cells and reducing necrosis in the tumor core when administered in conjunction with radiation therapy (Davis 2016). According to Gil-Gil et al. 2013, GBM cells generate the proangiogenic factor called VEGF which binds with its tyrosine kinase receptor on the surface of endothelial cells, initiating a signal cascade resulting in angiogenesis. Figure 7 demonstrates that Bevacizumab is easily able to penetrate the selectively permeable blood-brain barrier with a molecular weight of 149 kDa and binds with a high affinity to VEGF, sterically inhibiting the factor from binding to its receptors on endothelial cells and effectively reducing angiogenesis, inhibiting tumor growth, and reducing edema in the brain. | + | Bevacizumab (Avastin®) is a monoclonal antibody implemented in GBM chemotherapeutic regiments to target vascular endothelial growth factor (VEGF) and was approved by the FDA in 2009 after clinical trials had demonstrated excellent performance. The VEGF protein is needed for angiogenesis, a process that involves the synthesis of new vasculature from pre-existing vessels and occurs during wound healing and when cells are deficient in oxygen levels. The synthesis of new blood vessels among tumor cells mediated by VEGF leads to a greater blood and oxygen supply necessary for the proliferation of GBM cells (Gil-Gil et al. 2013). Avastin works to reduce vascular permeability and edema, enhancing delivery of oxygen to brain cells and reducing necrosis in the tumor core when administered in conjunction with radiation therapy (Davis 2016). According to Gil-Gil et al. 2013, GBM cells generate the proangiogenic factor called VEGF which binds with its tyrosine kinase receptor on the surface of endothelial cells, initiating a signal cascade resulting in angiogenesis. Figure 12 demonstrates that Bevacizumab is easily able to penetrate the selectively permeable blood-brain barrier with a molecular weight of 149 kDa and binds with a high affinity to VEGF, sterically inhibiting the factor from binding to its receptors on endothelial cells and effectively reducing angiogenesis, inhibiting tumor growth, and reducing edema in the brain. |
| {{ :avastin.png?500 |}} | {{ :avastin.png?500 |}} | ||
