glioblastoma

Question 1

grey matter

Answer 1

contains dendrites, cell bodies, axon terminals

Question 2

white matter

Answer 2

glial cells, myelinated axons

- where glioblastoma develops

Question 3

when do symptoms occur

Answer 3

when tumour is large enough so that it reaches grey matter or the inflammation reaches grey matter

• otherwise no symptoms as cognitive processes are not predominant in the white matter
• symptoms are sudden

Question 4

glioblastoma and types

Answer 4

• tumour develops in glial cells of white matter
• vascularization at tumour
• 3-4 months survival for malignant
• necrosis at tumour
  1) primary :de novo in origin
  2) secondary: arise from prexisiting lower grade gliomas

Question 5

tumour localization: temporal lobe

Answer 5

• hearing language speech production 30%

Question 6

tumour localization: parietal lobe

Answer 6

• sensory information, 16%

Question 7

tumour localization: frontal lobe

Answer 7

• cognitive processing, language memory 28%

Question 8

diagnosis (3)

Answer 8

biospy (dangerous)
neurological examination
MRI and CT scan

Question 9

low grade tumour

Answer 9

low inflammation

-necrosis in center

Question 10

high grade tumour

Answer 10

high inflammation in white

• shows accelerated growth due to inflammation
• necrotic

Question 11

why core becomes necrotic

Answer 11

growth rate and mass of tumour exeeds vascularization ability and rate that it can recruit blood vessels (outgrow blood supply)

Question 12

Pathophysiology: associated with poor survival

Answer 12

pathophysiology: loss of heterozygosity of chromosome 10q

Question 13

Pathophysiology: lack of tumour supression

Answer 13

deletion of p53

Question 14

Pathophysiology: upregulated in GBM, controls cell proliferation

Answer 14

EGFR

Question 15

Pathophysiology: controls angiogenesis, upregulated in GBM

Answer 15

VEGF

Question 16

Pathophysiology: upregulation allows for p53 supression escape as it binds and inhibits p53

Answer 16

MDM2 amplification

Question 17

Pathophysiology: DNA repair enzyme that contributes to tumour’s resistance to chemotherapy

Answer 17

MGMT amplification

Question 18

Grade 1 tumour

Answer 18

• benign slow growing

- long term survival, least likely to occur

Question 19

grade 2 tumour

Answer 19

• increased hypercellularity
• no necrosis, no vascular proliferation
• can recur as high grade tumour

Question 20

grade 3 tumour

Answer 20

• high rate of hyper cellularity
• no necrosis, no vascular proliferation
• high rate of reoccurence as high grade tumour

Question 21

grade 4 tumour

Answer 21

• necrosis, vascular proliferation

- very high mitosis and hypercellularity

Question 22

surgical intervention (new technique)

Answer 22

• laser shines near infared light which scatters differently for normal and abnormal cells
• surgeons know where to cut
• tumour removed and analyzed on mass spectrometer for molecular analysis

Question 23

Radiation Therapy ( new technique) - local control

Answer 23

brachytherapy-

• placing radiation (source) cathether to area requiring treatment immediately after surgery
• localized short range emissions to minimize damage
• 3-7 days
• can pass chemo wafers into same catheter to avoid passing through BBB

Question 24

Chemotherapy: methylating agent

Answer 24

Temozolomide (temodar)
- BBB permeable due to size
- converts intracellularly to methylating agent MITC
- methylates guanin bases which leads to instability, apoptosis during proliferation
MGMT is a repair enzyme that remove methyl groups from guanine
- counter to temozolomide

Question 25

Chemotherapy: neutralizing VEGF

Answer 25

bevacizumab (avastin)

• binds and neutralizes VEGF
• prevents angiogenesis and growth early on

Question 26

Personalized immunotherapy

Answer 26

DCvax L

• vaccine derived from own tumour cells
• DC cells extracted from blood and exposed to various tumour antigens
• take mature DC cells and inject back into blood
• report to local lymphnodes and T helper cells and program immune response

Question 27

ongoing difficulties

Answer 27

• BBB impentrability
• brain limited repair capacity
• brain damage likely
• drug resistance