Cancer Flashcards
What is the Warburg effect?
Cancer cells predominantly produce ATP/energy through glycolysis rather than the TCA cycle, even in the presence of oxygen
What is the process of tumor cell mobility?
(1) Extend lamellipod
(2) Stress fibers pull on the cell
(3) Tail end moves forward
What are the only three screening tests that increase longevity?
(1) Pap smears
(2) Mammograms
(3) Colorectal exams
What is the smallest size of tumor detectable on x-ray?
1 cm (1 billion cells, 30 divisions)
What are two categories of carcinomas and from what types of cells do they arise?
(1) Squamous cell carcinoma - cells of protective covering layers
(2) Adenocarcinomas - from cells lining ducts with secretory functions (glands)
From what types of cells do sarcomas arise?
Mesenchymal cells - bone, fat, blood vessels, muscle
What are three types of genes involved in cancer?
Proto-oncogenes
Tumor suppressors
Apoptosis regulator genes
How are oncogenes activated?
(1) Viral invasion - a provirus is inserted into vicinity of a proto-oncogene or a transduced proto-oncogene is mutated and inserted into the cell
(2) Genetic rearrangements - chromosomal translocations, gene amplification, somatic mutation
What is a gene amplified in 28% of primary breast carcinomas?
Her-2/neu - epidermal growth factor (EGF) receptor
How can HER-2 be treated?
Herceptin, an antibody against HER-2
How does RAS mutation cause cancer?
4
(1) Mutation in RAS inhibits (2) GTPase activating protein, (3) preventing cleavage of GTP and (4) leading to over-transduction of growth signal to nucleus
What is the cause of Burkitt Lymphoma?
t(8;14) involving IgH and c-MYC, leading to overexpression of c-MYC
c-MYC on C8
IgH on c14
What is the cause of chronic myelogenous leukemia (CML)?
t(9;22) involving ABL and BCR, leading to overexpression of ABL, a tyrosine kinase, and activation of growth factor signaling pathways
ABL on C9
BCR on C22
What are three tumor suppressor genes?
(1) p53
(2) BRCA1
(3) BAX
What are two cancers associated with BRCA1?
(1) Breast
(2) Ovarian
How does mutation of RF cause cancer?
(1) Normal RF binds E2F, preventing transition from G1 to S phase
(2) Normal RF is phosphorylated by cyclin-dependent kinase 4 (CDK4), leading to release of E2F
(3) Mutated RF leads to constitutively free E2F, so no regulation of trnasition from G1 to S phase
What mutated gene and protein are associated with hereditary nonpolyposis colorectal cancer (HNPPC)?
(1) MSH 2 gene
(2) DNA mismatch repair (MMR) protein
What are the two types of acute leukemia?
(1) Acute myeloid leukemia (AML)
2) Acute lymphoblastic leukemia (ALL
What are the two types of chronic leukemia?
(1) Chronic myeloid leukemia (CML)
2) Chronic lymphocytic leukemia (CLL
What defines acute leukemia?
(1) >20% blasts in bone marrow, which (2) crowd out hematopoiesis
What are the cellular characteristics of acute leukemia seen under microscope?
(1) Large immature cell
(2) Little cytoplasm
(3) Large or punched out nucleolus
What age groups to AML and ALL affect?
ALL - L for little, affects children
AML - M for middle age, affects adults 50+
What are the cellular characteristics of acute myeloid leukemia seen under microscope?
Auer rods (aggregation of myeloperoxidase)
What are AML markers?
6
(1) MPO - myeloperoxidase
(2) CD13
(3) CD33
(4) CD117
(5) HLA-DR
(6) CD15
What are monocytic markers of AML?
4
(1) CD64
(2) CD14
(3) CD11b
(4) CD11c
Which cytogenetic risk group has the most favorable prognosis?
t(15;17) - produces PML-RAR in acute promyelocytic leukemia, arresting cells in promyelocyte stage
inv(16) and t(8;21) also good
What is acute megakaryoblastic leukemia associated with?
Down syndrome, with acute megakaryoblastic leukemia arising before age 5
What clinical presentation is associated with acute monocytic leukemia?
Gum infiltration
What happens in tumor lysis syndrome and how is it treated?
6;4
(1) High cell turnover leading to (2) elevated uric acid, (3) renal failure, (4) increased K, (5) increased phosphate, and (6) decrease in calcium Treatment by (1) IV hydration with NaHCO3, (2) allopurinol for prevention of hemolysis, (3) hemodialysis, and (4) Rasburicase to break down uric acid
How is acute promyelocytic leukemia treated?
All-trans-retinoic acid (ATRA), which binds PML-RAR and causes blast maturation
What other disease is acute lymphoblastic leukemia associated with?
Down syndrome over the age of 5
Which B-ALL translocation is associated with a poor prognosis and seen in adults?
t(9;22) - Philadelphia chromosome
Which cell surface markers are characteristic of B-ALL?
(1) CD10
(2) CD19
(3) CD20
(4) CD 22
(5) cytoplasmic Ig
Which cell surface markers are characteristic of T-ALL?
CD2-8
What clinical characteristics are associated with T-ALL?
Appearance of a Thymic mass in Teenagers
What are the three phases of treatment for ALL?
(1) Induction (bring down counts) - Vincristine, Prednisone, Dauno
(2) Consolidation (eliminate remaining cancer cells) - Etoposide, Ara-C, methotrexate
(3) Continuation and maintenance
What is the difference between acute leukemia and chronic leukemia?
(1) Acute leukemia is a proliferation of blasts
(2) Chronic leukemia is a neoplastic proliferation of mature circulating lymphocytes
What are the four important types of chronic leukemia?
(1) Chronic lymphocytic leukemia (most important)
(2) Mantle cell leukemia
(3) Hairy cell leukemia
(4) Mycosis fungoides
What is chronic lymphocytic leukemia?
Neoplastic proliferation of naive, mature B cells
What is seen on a blood smear of chronic lymphoblastic leukemia?
Smudge cells, increased lymphocytes with low cytoplasm
What cell surface markers are expressed on B cells in chronic lymphocytic leukemia?
CD5 and CD20
What are three complications of CLL?
(1) Hypogammaglobulinemia
(2) Autoimmune hemolytic anemia
(3) Richter’s transformation to aggressive large cell lymphoma
What is treatment for CLL?
(1) Rituximab - monoclonal antibody against CD20 (reducin mah B)
(2) Chemotherapy + rituximab
What are four myeloproliferative disorders?
(1) Chronic myeloid leukemia (CML)
(2) Polycythemia vera
(3) Essential thrombocytopenia
(4) Myelofibrosis
What are myeloproliferative disorders?
2
(1) Neoplastic proliferation of mature cells of myeloid lineage (2) occurring in late adulthood
What are three complications of myeloproliferative disorders?
(1) Increased risk of hyperuricemia/gout
(2) Progression to bone marrow fibrosis from burnout
(3) Transformation to acute leukemia
Which cells are increased in chronic myeloid leukemia?
(1) Granulocytes and precursors
(2) Basophils
What is a common clinical manifestation of CML?
Splenomegaly, suggesting transformation to accelerated phase of disease (leading to acute leukemia)
How can chronic myeloid leukemia be distinguished from a leukemoid reaction?
(1) Negative LAP
(2) Increased basophils
(3) t(9;22)
What is treatment for CML?
Imatinib - a tyrosine kinase inhibitor
What is the cause of chronic myeloid leukemia?
t(9;22) - Philadelphia chromosome
Which cells are increased in polycythemia vera?
Mature myeloid cells, especially RBCs (also granulocytes and platelets)
How does polycythemia vera present clinically?
4
(1) Blurry vision and headache
(2) Flushed face
(3) Itching, especially after bathing
(4) Increased risk of venous thrombosis (Budd Chiari syndrome - hepatic vein thrombosis)
How can polycythemia vera be diagnosed?
3
(1) High RBC count
(2) Low EPO - high in reactive polycythemia
(3) JAK2 kinase mutation
How is polycythemia vera treated?
(1) Phlebotomy - lowers hematocrit
(2) Hydroxyurea - decreases RBC mass and risk of thromosis
What cells are increased in essential thrombocytosis?
Platelets and megakaryocytes
What mutation is essential thrombocytosis associated with?
JAK2 kinase
How is essential thrombocytosis treated?
2
(1) Aspirin
(2) Hydroxyurea
What is myelofibrosis?
(1) A form of chronic myeloid leukemia with (2) fibrosis of the bone marrow (3) due to excessive platelet-derived growth factor (PDGF) (4) produced by increased megakaryocytes
What leukemias is JAK2 kinase associated with?
(1) Polycythemia vera
(2) Essential thrombocytosis
(3) Myelofibrosis
