Cancer Flashcards
State the cancers associated with ebstein Barr virus
Burkit’s lymphoma
State the cancers associated with hepatitis
Liver cancer
State the viruses associated with HIV
Lymphoma
Kaposi’s sarcoma
State the viruses associated with H pylori
Lymphoma of the stomach
What meant by immunosurveillance
Immunosurveillance is a term used to describe the processes by which cells of the immune system detect cancer and get rid of it. A failure of this system leads to cancer
What is an increase in CD8 cells associated with in some tumors?
Good prognosis
What are the three possible outcomes of cancer
Elimination, equilibrium, Escape,
What is the RAG gene?
Recombination activating gene. It encodes enzymes needed for B and T cell activation. improved prgnosis of cancer patients
What does interferon gamma do in relation to cancer?
Anti tumor cytokines
When fighting cancer cells, how are NK cells able to recognize that they are abnormal.
They do not bind to the MHC I receptor on NK cells.
Describe the cellular events in the process of eliminating a cancer cell.
- NK cells detect cancer cells and cause their lysis.
- Tumor antigens are picked up by APC and presented to T cytotoxic cells
- T cytotoxic cells kill the remainder of the cells that escaped NK cells by secreting performing and granzymes.
Write out the signals of T cell activation
- Signal 1= TCR binds to MHC II
- Signal 2= CD28 on T cell binds to B7 (CD80/86) on APC. this is a positive cistomulatiry signal leading to T cell proliferation
- Signal 3= CTLA4 binds to B7 instead of CD28, inhibiting T cell proliferation (negative costimulatoey signal) to preserve immune balance
Why are immune co inhibitory cells important
To prevent the hyperactivity of the immune cells. Cells like CTLA4 and PD-1 are known as immune “checkpoints”
Other the CTLA4, what is an important immune checkpoint?
PD-1 receptor (programmed death receptor). It’s ligand are PD-1 and PD-2 on APC. Cause T cell inactivation
Which specific cells do PD-1 and CTLA4 target?
CTLA4 targets CD4
PD-1 targets CD8
What is meant by self tolerance?
The ability of the immune system to recognize self antigens from forgein antigens
What is the main function of the Treg?
Crucial for the maintenance of self tolerance
What is the transcription factor unique to T regs that indicate their maturity?
FOXP3
What are the two types of Tregs and what is the difference between them
Natural T reg: produced in the thymus, matures fully in the thymus.
Induced T reg: procured in thymus, however doesn’t mature until it comes in contact with an antigen, and expressed FOXP3
What does FOXP3 activate the transcription of?
CTLA4
State two ways in which Tregs perform their immune tolerance function
- Increase transcription of inhibitory cytokines such as IL10, 35, TGF-Beta
- Increase transcription of CTLA4
When can the immunosuppression of Tregs be a bad thing?
It could be a cancer’s method to escape immunosurveillance
What happens if we have a mutation in FOXP3?
IPEX: immunodeficiency, polyendocrinopathy, enteropathy, x linked
What do non fcuntionig t regs lead to?
AUTOIMMUNE DISEASE. (because t regs function is central tolerance)
Does cancer infiltration with Tregs provide a good or poor prognosis?
Poor. This is because Tregs inhibit immune response. Therefore, the cancer may find a way to evade the immune system b
What is the effect of TGF Beta on immune cells?
Decreases activation of T cells and macrophages
What are the mechanisms cancer cells used to evade immune system
- Down regulation of MHCI
- increase TGF Bets
- Increase Treg
What were the monoclonal antibodies given to try to fight against cancers?
Monoclonal antibodies for CTLA4 and
Is the antigenic variation of tumor cells beneficial or harmful to the host?
Beneficial, as it allows for a new immune response
Tumor editing is one of the most difficult clinically relevant problems to overcome in the course of tumor therapy. Which one of the following accounts for the mechanism of tumor editing?
Survival of tumors with low expression of class I MHC molecules
Cancer associated with HBV?
Hepatocellular carcinoma
What are the dangerous p, cancerous tyoes of HPV?
16,18
What are the cancers associated with ebestein Barr virus
Burkkit’s lymphoma
Nasopharyngeal carcinoma
What are the cancers associated with human heroes virus 8
Kaposi’s sarcoma (especially in HIV)
What are the cancers associated with human t lymphotropic virus
Adult t-cell leukemia/lymphoma
What are the cancers associated with Merkle cell polyoma virus
merciless cell carcinoma
Why are viruses able to cause cancer
PERSISTENT INFECTION
Can RNA viruses integrate their DNA into host cell?
No. RNA cannot be integrated into DNA.
Explain how retroviruses integrate their genome into DNA.
Retroviruses are RNA viruses that contain REVERSE TRANSCRIPTASE. therefore they convert into a DNA sequence and integrate themselves into the host genome’s DNA
What is a transformed cell?
A normal cell transformed into a malignant cell by a viral genome
State the 5 hallmarks of cancer.
Sustained angiogenesis, evading apoptosis, self suffiency on growth signals, insensitivity to anti growth signals, invasivon andmetastasis,
Why are virus associated cancers called abortive infections?
This is because once the viral genome is integrated into the host DNA? Virus no longer replication
What are the types of papilloma viruses that can infect man? And what do they infect
Alpha; skin and mucous membranes
beta, gamma, mu, nu: skin
Why were we able to develop a vaccine to HPV?
Because it is a stable virus that does not mutate
How does low risk alpha HPV present itself?
Warts
What is the TNM staging?
The staging done to determine the severity of a cancer
State each score given in the TNM staging and its meaning
- T= tumor size
T1: up 2cm, T2: up to 5cm, T3: more than 5cm, T4: infiltrating chest wall or skin) - N= lymph node involvement
N0, N1: 1 to 3 lymph nodes, N2: up to 9 lymph nodes, N3: more than 9)
3: M= presence of metastasis? (M0,M1)
Which tumors have a high level of carcinogenic embryonic antigen?
Colorectal cancers
Pancreatic cancers
Breast and gastric tumors
Which tumors have a high level of alpha fetoprotein?
Liver cancer
What is herceptin?
her 2 antibody, given in cases of breast cancer .
What is the difference between leukemia and lymphoma?
Lymphoma: malignancy in non circulating cells(tissue lymphocytes). Affect lymph nodes.
Leukemia: malignancy in circulating cells. Affect blood and bone marrow
What is the cell of origin of a lymphoma?
Tissue lymphocytes
What is the cell of origin of myeloid leukemia?
Granulocytes
What is the cell of origin of lymphocytic leukemia?
Marrow lymphocytes
What is the cell of origin of multiple myeloma
Plasma cells
What are the grades of tumor differentiation?
1= Well differentiated, resembles tissue of origin 2= Intermediate 3= undifferentiated
What is the most common benign tumor of the female breast?
Fibroadenoma. A new growth composed of fibrous and glandular tissue
What are the two types of fibroadenoma?
Intracanalicular: a lot of fibrous storma surrounding the glands, compressing them and giving them a slit like appearance.
Pericanalicualar: fibrous stroma around the gland, however glands are still patent.
Gross picture of fibroadenoma?
Grey, white with yellow spots, solitary, freely mobile, 1 to 10cm
What is the clinical presentation of introductal papilloma
Serous of bloody nipple discharge, subareolar tumor
What is the gross picture of introductal papilloma
Intraductal hemorrhage, branching papillary growth within a duct
How can we tell by using the immunohistochemical marker CALPONIN that intraductal papilloma is benign and not malignant?
calponin is the special stain for myoepithelial cells. Myoepithelial cells appear normal with no invasion, indicating a benign lesion
What are the factors that increase the likelihood of breast cancer?
Obesity, high lipid diet,
EXCESS OESTROGEN. (Endogenous or exogenous).
Example: women who have had a menstrual cycle for a long time are under the effect of oestrogen for more years and are more likely to develop breast cancer.
What is the differential diagnosis of a woman with a benign mass in her breast?
Fibroadenoma
Intraductal papilloma
What is the differential diagnosis of a woman with a cancerous mass in her breast?
ductal carcinoma (in situ or invasive)lobular carcinoma (in situ or invasive)
What is a marker that we can use to differentiate between lobular carcinoma and invasive ductal carcinoma?
E cadherin. It is lost in lobular carcinoma but persevered in invasive ductal carcinoma
What does ductal carcinoma in situ affect
Ductal epithelial cells
What does lobular carcinoma in situ affect
Terminal acini and ducts
What are the 3 general most important clinical presentations of breast cancer?
- Nipple retraction
- Cancer en cuirasse ( fixation of the breast and infiltration to pectoralis minor)
- Peau d’orange
Which is more common, invasive ductal carcinoma or invasive lobular carcinoma?
Ductal
Does invasive Lobular carcinoma usually occur bilaterally or only one one side?
Bilateral
Does the presence of oestrogen and progesterone receptors in cancers indicate a good or bad prognosis?
Good prognosis, the tumor will most likely regress after hormonal therapy.
What is CD34?
It is a molecule present ONLY on stem cells. An absence of CD34 means that it is not a stem cell.
What is a property of the bone marrow that allows transplanted stem cells to stay adherent to the stroma?
Stroma have receptors for the stem cells of the bone marrow and form a “home” environment for them
What is the function of erythropoietin?
Prevent apoptosis and destruction of RBCs
What stimulates the production of erythropoietin?
An episode of stress on blood supply aka. Blood loss
What are the negative regulators of hematopoiesis?
TGF beta and MIP alpha
What is the positive regulator of WBCs to prolong their survival during stress in the body
Growth colony stimulating factor, allows neutrophils to live longer to fight against bacterial infections
What is thromobpoietin?
A substance released. H the liver to promote platelet production
What are the viral proteins in kaposi’s sarcoma that cause cellular deregulation by inactivating p53 and rb gene?
LANA (latent associated nuclear antigen)
What is the clinical picture of lymphoma?
Lymphadenopathy since the malignant lymphocytes accumulate in lymph nodes
What are the two types of lymphoma
Hodgkin and non Hodgkin’s lymphoma
What is the difference between Hodgkin and non Hodgkin’s lymphoma?
Hodgkin’s lymphoma contain what is called Reed stern berg cells
What are the findings in leukemia due to bone marrow failure?
Thrombocytopenia, neutropenia, anemia
What is the site we usually choose to do a bone marrow aspirate or trephine?
Posterior superior iliac spine
What are the two types of light chains of the antibodies carried on the B cel surface?
Kappa or lambda, NEVER both.
How can we prove the single cell theory of malignancy when it comes to lymphomas?
Ina regular infection, we get a polyclonal action of B cells and get an increase in both kappa and lambda light chains. Wheras in lymphomas, only one of them increases, related to the malignant cell of origin. This is what proves that malignancies could be derived from a single cell.
Describe the features and clinical presentation of acute leukemia
Malignant IMMATURE wbcs (blast cells). This is because they undergo a block of differentiation. Since cells are immature we have a deficiency in functioning wbc despite their high count (leukocytosis) however 70% of them are immature. -Presents with bone marrow failure: thrombocytopenia, anemia, neutropenia.
- thrombocytopenia leads to ecchymosis (bleeding under the skin) due to low platelet count
- The disease progresses relatively quickly.
What is the mutation commonly found in patients of acute leukemia
PML-RARA (reciprocal translocation between chromosomes 15 and 17)
Describe the features and clinical presentation of acute leukemia
- slowly progressive
- cells are mature but patient gets organomegaly (spleen+ liver) due to a cellular burden as a result of lack of apoptosis
What is the mutation commonly found in patients of chronic leukemia
Philadelphia translocation (9:22) BCR-ABL
What is the chromosomal translocation underwent in burkkit’s lymphoma?
IgH-myc (8;14 or 2 or 22)
What is the chromosomal translocation that happens in follicular NHL?
IgH- BCR-2
What is APL?
Acute promyelocytic leukemia (APL) is an aggressive type of acute myeloid leukemia in which there is an ACCUMULATION OF PROMYELOCYTES. This build up of promyelocytes leads to a shortage of normal white and red blood cells and platelets in the body
How can we overcome the block of differentiation in AML M3 or acute promyelocytic leukemia?
conjunction with cytotoxic agents. Treatment with high doses of retinoic acid in conjunction with cytotoxic agents relieves PML-RARA inhibition and allows differentiation of leukaemic cells
When is RAS protein activated or inactived? What controls this?
RAS is activated: when bound to GTP
RAS is inactived: when bound to GDP.
this is controlled by GAPS; GTPase activating proteins. Breaks down GTP to GDP
Give an example of GTPase activating protein and what would happen in case of it’a disfunction
NF-1. There would be excess RAS protein activity
What signalling transduction pathway abnormalities are the BCR- ABL and the PML-RARA translocations responsible for?
BCR-ABL: aberrant tyrosine kinase activity (increased)
PML-RARA: increase RAS protein -MAP Kinase pathway activation
What could be the cause of increased RAS protein activity? Which hematological malignancy does this occur in?
Point mutation or loss of NF-1 (a GAPS protein).
What is the mode of action of imatinib/ gleevec
mode of action of imatinib?
What is a band cell?
immature lymphocyte
What is a trephine biopsy
A
What is the percentage of blasts in the peripheral blood above which we diagnose with leukemia?
20%.
What is the natural progression of CML after taking imatinib for 2 years
Transformation into AML
How does p53 function to inhibit tumor progression
p53 induces transcription of cell-cycle inhibitorygenes DNA-repair genes (eg GADD45) and pro-apoptotic genes (eg Bax, Puma, Noxa)
Does burkit’s lymphoma grow quickly? Can it be cured?
Yes, up to 75%