Brain Tumors 2
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A)The major cause of symptoms commonly seen in Brain tumors is?
B) What are some of the symptoms (non-specific)? -
A)Increase Crainal Pressure generated because of the increase in cell number in the confined area of the skull
B)Headache, Changes in levels of consciousness, vomitting, and/or nausea. -
A)Temporal Lobe Tumors commonly are associated with?
B)If the tumor is on the dominant hemisphere in the Temporal Lobe, what also could occur -
A)Seizures
B) Speech or Language dysfunction. - What are some common Primary Brain tumors?
- Astrocytomas (GBM being one grade), Menigiomas, Ependymomas, Oligodendrogliomas, etc.
- What are the four most common histologic origins for Secondary Brain Tumor?
- Lung, Breast, Skin, and Colon. Lung being the most common.
- Why is the Prognosis for secondary brain tumors typically poor even though surgery is fairly easy and the cancers are fairly responsive to the treatment?
- The discovery of the tumor usually occurs during the later stages of the Primary source of the tumor, i.e. the breats or lungs, which means that the patient has a poor prognosis regardless of the brain tumor.
- What is a common difference between locations of Primary and Secondary Brain Tumors?
- Primary are usually more infiltrative and do not have discrete borders, while the seondary tumors typically settle along the White-Grey border due to the high vascularization in those areas due to the MCA.
- The most common Malignant Primary Brain Tumor is?
- Glioblastoma Multiforme, or Grade IV Astrocytoma.
- At what grade are Astrocytes considered to be malignant?
- Typically at Grade III, but remember that lower grades can progress into type III's.
- Define Pleomorphic
- Variable cell shape in a cell type that typically would have similar shapes and characteristics.
- With respect to histological slides, what does Necrosis mean?
- Generalized cell death
- What Phenotypic Features of GBM make it difficult to treat and drive this Morbidity and mortality?
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1)Angiogenesis
2) Proliferation and Survival
3)Invasion
4) although not mentioned specifically in lecture, the fact that it is in the brain makes it more difficult to treat than normal (BBB for chemotherapy and potential for devastating collateral damage in surgical procedures) - What are the two ways to develop GBM?
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1) De Novo ("from a new thing")
2) Transformation from a lower grade tumor - What two genes are commonly associated, but not limited to, De Novo GBM?
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1)Amplification of the EGFR (a gain of function mutation, i.e only requires one mutation)
2)Loss of the Tumor Repressor Gene, PTEN, via LOH 10 (loss of heterozygosity of chromosome 10) (a loss of function mutation requiring both copies of the gene to be ineffective) - What are some common mechanisms of Radiation Therapy action?
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1)Breaking the DNA itself
2)creation of free radicals with break the DNA
3)Breaking the double strands. - What is the real objective in brain cancer treatment?
- Prolonging the quality of life, ie. turning the cancer into a chronic, but manageable, disease.
- What is the main reason the Brain tumors are considered Gliomas?
- They present with cell surface antigens, like Glial Fibrillary Acidic Protein (GFAP) and Myelin Basic Protein (MBP), that are common and specific to glial cells.
- Why does one actually care about the specific cellular origin of the tumor?
- To design the appropriate treatment that will selectively inhibit/destroy, the cells associated with that specific line of origin.
- What is the normal function of p53?
- To prevent entry into the S phase of cell division. It is the "guardian of the genome"
- What are the three characteristics common to all types of brain tumors, and what is the characteristic found only in type IV Astrocytomas?
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1)Pleomorphism/nuclear atypia
2)Abnormal Mitosis
3)Necrosis - remember, this only means generalized cell death
4)Neovascularization (only found in grade IV, but keep in mind that angiogenesis is common in all tumors, its the neovasculartization that is unique) - Oligodendrogliomas are commonly found where and appear similar to?
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A)White matter - remember, Oligo's make the myelin coats
B)'fried eggs" - Ependymomas have a direct affect on what parts of the brain?
- The ventricles
- In what way does the exaggeration of the normal Cerebral production of Glutamate in brain tumors decrease radiation therapy techniques and how does Azulfidine (Sulfasalazine) overcome this?
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Neurons -> release Glu -> absorbed by Glial cells.
In Gliomas, the glial cells release Glu (which is cytotoxic) via anti-transporters of Cystine. Cys is then used as a precussor for Glutathione, which is a cellular antioxidant. Since radiation therapy relies on free-radicals, the exaggerated production of Glu leads to more Glutathione which means the free radicals are dealt with easily.
Axulfidine inhibits the uptake of cys and the production of Glutathione. - How do Glial Cells migrate, and how does scorpion venom play into this?
- Cells actually shrink by pumping out K and Cl (along with water). This decreases cell size and allows the cells to move easier in the brain and outside the brain. The scorpion venom, Chlorotoxin, inhibits Cl secretion.