Biology 207 Biology of Cancer
Lecture 17 "Brain Cancers" Spring 2004
Reading: Lemonick, “The tumor war” TIME 150, 46-53
Web sites: American Brain Tumor Association: http://www.abta.org
Oncolink: http://.oncolink.upenn.edu
Lecture Outline
1. Statistics and Risk factors
2. Classification
3. Astrocytomas
4. Diagnosis
5. Treatment/Blood-Brain Barrier
Lecture:
1. A. Statistics:
· In 1997, 18,000 new brain tumors diagnosed; 50% increase from 10 years ago
· Account for only 1.4% of cancers in U.S.
· Not a major cancer, however most deadly because they interfere with essential life functions
· Do not metastasize to other parts of the body
B. Risk factors
· Radiation exposure
· Impaired immune systems, HIV, other cancers
· Heredity
· Head trauma NOT a risk factor
2. Classification
Primary brain tumors: those that start in the brain
Secondary brain tumors: due to metastasis of other cancers to the brain
· Primary tumors are classed based on cell type of origin
Most common brain tumors:
· Astrocytomas=gliomas
· Arise from astrocytes, which are glial cells
· These make up the blood-brain barrier and contribute to nutrition of the central nervous system
· Glial cells do divide in adults; nerve cells do not divide in adult
· Cancers of nerve cells only occur in children and are called Neuroblastomas
Secondary brain tumors:
· Most commonly spread from breast and lung
· Colon cancers and melanomas can also spread to the brain
· Cells of secondary tumor resemble the cells of the organ where the tumor started, not brain cells
3. Astrocytomas
World Health Organization tumor grading system
Tumor grades 1à 4
1= slowest growing
4= fastest growing
Grade 1
· Astrocytic tumor cells usually normal looking
· Observe cell proliferation
· Produce epileptic seizures as their only symptom
· Can become quite large and increased pressure inside skull can lead to headaches, paralysis, personality change, coma and death
· Prognosis good
· Radiation therapy not recommended
Grade 2
· Tumor cells slightly abnormal in appearance as well as number
· No mitotic (dividing) cells usually observed
· No necrosis (dead tissue)
· Usually biopsied, not removed
· Radiation treatment usually recommended to shrink tumor
Grade 3
· "Malignant astrocytomas"--Can spread to other regions of brain or spine but not to other parts of the body
· Observe "contrast enhancement" on CT and MRI scans
· Cells are abnormal in appearance
· Show evidence of mitosis
· Cells in the tumor invade brain tissue
· Confirm diagnosis with surgery or stereotactic biopsy
· Follow up with radiation or chemotherapy
· Average survival 18 months without treatment
Grade 4
· Called glioblastomas
· Most malignant form
· Made of cells that infiltrate brain tissue
· Mitotic cells frequently observed
· Regions of dead tissue seen especially where growth of tumor has outpaced blood supply
· Tumors induce angiogenesis, however new blood vessels may be abnormal
· Obvious mass seen on CT and MRI scans
· Very poor prognosis: survival 17 weeks with no treatment, about 1 year with certain treatments
· Prognosis depends on age and performance status
4. Diagnosis of brain tumors:
Signs and symptoms of brain tumors:
· Depend on location in brain
· Size of tumor
May include:
· Paralysis/numbness
· Mood swings
· Seizures
· Loss of balance
· Impaired vision
Generally a tumor on one side causes symptoms and impairment on opposite side; exception is cerebellum
Tumor may place pressure on the brain or cause build-up of fluid, leading to headaches. Headaches are most common presenting symptom
Neurological exam: Office visit to specialist doctor (Neurologist) to assess reflexes and brain function.
Scans: CT and MRI
· Inject a dye to make abnormal tissue more obvious
· Dyes concentrate more in disease tissues due to leakiness of blood vessels in and around brain tumors
· CT better for tumors showing calcification (calcium deposits due to erosion of bone)
· MRI better for small tumors, tumors next to bone, brain stem tumors
· Low grade and metastatic tumors
CT scan=Computerized tomography
· X-ray device combined with a computer
· Patient lays on a table that slides into an opening like a doughnut hole in the scanner
· X-rays penetrate brain from many directions, thousands of thin cross sections are fed into a computer that constructs a picture
MRI scan=Magnetic resonance imaging
· Tunnel shaped piece of equipment
· Magnetic field surrounds the head
· Radio frequency pulse introduced; does not involve X-rays
· Magnetic field causes atoms in brain to change direction
· Radio frequency pulse causes another change in direction
· Pulse stops; during relaxation, atoms give off energy in different amounts and at different intervals
· Antennas pick up signals and feed them into a computer that assembles an image
Follow-up may involve biopsy
· Surgery to remove tumor
· Stereotactic biopsy=remove small piece of tissue with thin needle
5. Treatment options
Survival depends on
· Type of tumor
· Location of tumor
Therapy for Astrocytomas:
· Generally not curable
· Surgery often done after MRI or CT scan
· Radiation: External beam or internal implants
· Chemotherapy: Options still in clinical trials
· Experimental therapies: immunotherapies, gene therapies
Problems with chemotherapies and other experimental therapies:
Blood--brain barrier--Blood vessels in the brain are not leaky because of connections between endothelial cells lining the blood vessels.
· Most drugs can't diffuse from blood to get to tumor.
· New drugs make blood vessels leaky so they can take up drugs
Example: Bradykinin analog RMP-7.
· Bradykinin is naturally occurring body peptide with hormone action.
· Analog can make blood-brain barrier leaky as site of tumors but not in normal regions of brain.
· Combine RMP-7 with chemotherapeutic drug to deliver to brain tumor
Other strategies involve delivery of drugs with liposomes (lipid coat around drug molecules); fats (lipids) can cross the blood-brain barrier
Other approaches try to recruit patient's own immune system to attack brain cancer="immunotherapy"
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