Cancer and Apoptosis
What is the difference between a benign and malignant tumor.
Benign is located in one part of the body, maligant spreads to other parts of the body.
Explain in certain cancer cells where multi-drug resistant proteins are located and how they make cancer cells resistant to chemotherapy drugs.
Multi-drug resistant proteins are integral proteins on the cell membrane, and they pump out any chemotherapy drug that enters the cell, therefore drug is not in the cell long enough to cause apoptosis.
1. What is the difference between a sarcoma and a carcinoma.
•Solid tumors can be classified as carcinomas which are solid tumors in organs ( lung, colon, breast, pancreas,etc.) and sarcomas found in connective tissue and muscles ( melanoma ( skin cancer), osteosarcoma ( bone cancer).
Daily Double -Which part of the body do MM, leukemia, lymphoma originate in
1. MM and leukemia - bone marrow
2. Lymphoma - lymph nodes
What is the lymphatic system and describe the components of the lymphatic system
•Lymphatic system is a network of blood vessels and organs that filter out pathogens.
•Lymph fluid contains plasma which is liquid blood. Plasma contains water, nutrients and pathogens. The lymph fluid travels to the lymph nodes where the B and T cells in the lymph nodes kill the bacteria and now the filtered lymph fluid is returned to the circulatory system.
•Besides the lymph nodes other organs of the lymphatic system include
•Bone Marrow where red and white blood cells are produced.
•Thymus where T cells mature
•Spleen filters your blood and removes damaged cells. Spleen also stores red blood cells and platelets as a reservior if your body needs them.
Explain the steps of metastasis.
. Tunor cells break off the tumor
2. Enter blood vessel (intravasaction)
3. Those that survive in the blood vessel will eventualy exit the blood vessel (extravasaction) and now have moved to a different part of the body.
What is the difference between normoxic and hypoxic regions in tumors, and which regions of the tumor are normoxic and which regions are hypoxic.
1. Normoxic regions have oxygen levels of 5 to 1 % , while hypoxic regions have oxygen levels below 1%.
2. The periphery or edges of the tumor are normoxic while the interior of the tumor is hypoxic.
Daily Double - What are the six hallmarks of cancer
1. Evade tumor suppressors
2. Sustained Cell Signaling
3. Evade apoptosis
4. Replicative immortality
5. Angiogenis
6. Metastasis
In MM describe which cells overproliferate and what are the complications that result from this
•Over-production of one antibody subtype instead of production of various sub-types ( for example all the plasma cells in a MM patient might only produce IgA sub-type, but not IgE, IgD, IgG, or IgM) therefore this can lead to a compromised immune system.
•Over-production of misfolded light chains can lead to AL ( antibody light chain) amyloidosis which can result in these misfolded light chains to aggregate and go into circulation and damage organs such as: heart, kidney, GI tract, and liver.
•Over-proliferation of MM cells crowd out and impair production of healthy red blood cells, white blood cells and platelets in the bone marrow.
Describe what lymphoma is and where does it occur.
•Lymphoma is abnormal growth and development of lymphocyte cells ( B cells and T cells in the lymphatic system) it occurs in the lymph nodes
For the following either select apoptosis, necrosis or both
1. ATP is depleted
2. Cell shrinks
3.DNA damaged
4. Cell swells
5. Organelles damaged
6. Causes inflammation
7 Pathological or physiological
8. Involves caspase enzymes
9. Caused by heart attack, strike, bacterial infection
10. Involves macrophages to clear up debris after process is complete
11. involves p53
1.N
2. A
3. B
4. N
5. B
6. N
7. A
8. A
9. N
10. A
Describe three ways p53 can act as a tumor suppressor.
1. Promote intrinsic apoptosis by causing mitochondria to release cytochrome C.
2. Repair damaged DNA
3. Cause G1/S cell cycle arrest that will result in errors in the cell being fixed or if they cannot be fixed apoptosis will occur.
Describe the events that occur in stages 1-4 of cancer
•Stage 1 – tumor is small and is localized in one part of the body
•Stage 2 – tumor has become larger and has spread to surrounding tissues.
•Stage 3 – tumor has spread to surrounding lymph nodes.
•Stage 4 tumor has metasized throughout the body.
Describe in detail the CRAB condition associated with MM
•C – Calcium dysfunction – MM microenvironment can lead to production of cytokines that lead to release of calcium from osteoclasts cells ( cells that break bone). Hypercalcemia leads to neuronal issues and dehydration.
•R – Renal failure – Kidney's over-work to filter out both excess calcium and light chain antibodies in circulation.
•A – Anemia – impaired production of red blood cells can lead to decreased delivery of oxygen to cells
•B – bone lesions – overactivation of osteoclasts by cytokines released by MM tumor microenvironment can lead to bone breaks in spine, pelvis, ribs, and skull.
Describe why proteasome inhibitors are effective in treating MM
MM cells produce a lot of misfolded light chain antibodies, by inhibiting the proteasome you increase the level of misfolded proteins to a level that is toxic tp the MM resulting in apoptosis.
Provide three scenarios how aberrant AR signaling can lead to prostate cancer
Excess production of testosterone and/or DHT
•A mutation in the AR that will cause it to be active even if the DHT ligand is not bound to the AR.
•If the AR is mutated or it attracts other proteins that lead to increased transcription rates of genes for cell proliferation.
Provide two treatments that will prevent over-activation of the HER2 RTK in HER2+ breast cancer.
1. Kinase inhibitors that prevent phosphorylation of the tyrosine's.
2. Antibody that blocks dimerization, therefore activation of the RTK will not occur.
Describe how the TNM system is used to classify what stage a cancer is
•T ( tumor ) T0 – no tumor T4- large tumor
•N (lymph node) N0- tumor not found in lymph node N3- tumor has spread extensively into lymph node
M –( Metastasis) M0- No metastasis M1- Metastasis
1. What are the two types of blood stems cells that can over-proliferate and result in leukemia.
2. What are the health consequences associated with leukemia
1. myeloid or lymphoid cells.
2. •Leukemia leads to defective white blood cells ( weaken immune system), defective red blood cells ( anemia) , and defective platelets ( increased bleeding, decreased wound healing).
Explain why tyrosine kinase inhibitors are effective in treating CML
•Tyrosine kinase inhibitors are competive inhibitors for ATP, therefore preventing phosphorylation of ABL making the ABL an inactive kinase and as a result slowing down cell proliferation.
Compare and contrast the intrinsic and extrinsic pathways of apoptosis.
Intrinsic pathway is activated by internal stresses ( nutrient deprivation, DNA damage, mis-folded proteins) that will activate p53, then p53 will result in the release of cytochrome C from the mitochondria. The cytochrome C will activate caspase enzymes that will degrade the DNA, proteins, cytoskeleton, and organelles that will then result in the cell shrinking into blebs that will be phagocytosed by macrophages.
Extrinsic apoptosis, the target cell receives a signal from outside the cell ( death signal ) that will bind to the death receptor on the target cell this will lead to release of cytochrome C from the mitochondria ( p53 independent) The cytochrome C will activate caspase enzymes that will degrade the DNA, proteins, cytoskeleton, and organelles that will then result in the cell shrinking into blebs that will be phagocytosed by macrophages.
BOTH lead to release of cytochrome C from the mitochondria and activate caspases that lead to apoptosis
Provide three treatment scenarios for targeting the ER in breast cancer.
Excess production of estrogen ligand
•A mutation in the estrogen receptor that will cause it to be active even if the estrogen ligand is not bound to the estrogen receptor
•If the dimerized estrogen receptor is mutated or it attracts other proteins that lead to increased transcription rates of genes for cell proliferation.
What are the three types of cells that make up blood
1. Red blood cells - produce hemoglobin to deliver oxygen to red blood cells.
2. White blood cells - fight infections
3. Platelets - involved in blood clotting
Describe how CML is caused
•Caused by a chromosomal translocation between chromosome 9 which carries the ABL gene ( codes for tyrosine kinase protein that is involved in activating proteins involved in cell signaling) and chromosome 22 which carries the BCR gene).
•This results in a fusion BCR-ABL protein.
•The normal ABL protein is either in an open conformation ( active form) or closed conformation ( inactive form), thus its activity is regulated.
•The fusion BCR- ABL protein is always in the open conformation, therefore it is always an active tyrosine kinase leading to unregulated cellular proliferation.
Compare and Contrast Hodgins's lymphoma with Non-Hodgins's lymphoma
•Hodgins Lymphoma is when B cells become abnormal and proliferate rapidly. These B cells take on a unique morphology and are often called Reed-Sternberg cells.
•In Hodgins Lymphoma the Reed-Sternberg cells spread in an orderly manner to adjacent lymph nodes.
•Non- Hodgins Lymphoma is when either the B cells or T cells become abnormal and proliferate rapidly.
•In Non- Hodgins Lymphoma cells spread in a disorderly manner to distant parts of the body.
•Non-Hodgins Lymphoma is more common and has a worse prognosis than Hodgins Lymphoma.
•Hodgins Lymphoma is associated more with younger adults, while Non-Hodgins Lymphoma is more common in older adults.
•Symptoms of Lymphoma include: swollen lymph nodes, fever, fatigue, weight loss, itch skin