Neoplasia 2 h/o Flashcards
BRCA-1 and 2 are caretaker genes, what does this mean?
Caretaker genes
-affect genetic instability and DNA repair
How do follicular B cell lymphomas avoid apoptosis?
Fusion of the Bcl-2 gene from chromosome 18 to the active IgH locus on chromosome 14 leads to overproduction of Bcl-2 (anti-apoptotic protein)
How does follicular lymphoma generally present in patients?
- Very slowly developing enlargement of lymph nodes
- Not painful
- Avg patient age is 60
- No treatment
What two factors normally inhibit angiogenesis?
- Thrombospondin-1 (induced by p53)
- VHL (Von Hippel Lindau): destroys HIF-1, preventing the formation of VEGF
What factors play a role in the angiogenic switch?
- HIF-1 alpha
- basic FGF
- loss of p53
- decreased thrombomodulin-1
- overcoming anti-angiogenic factors (angiostatin,endostatin, vasculostatin)
What is the function of the drug Bevacizumab?
Anti-VEGF agent used in tumor suppression
-only mildly helpful in most cases
T/F sustained angiogenesis is essential for tumors to grow larger than 2 mm, but inhibiting this has limited efficacy in controlling cancer
True
-a million tiny foci of cancer (<2mm) can have lethal effect without sustained angiogenesis
What are the steps of invasion by malignancy?
1) Detachment of tumor cells from each other (due to downregulation of E-Cadherin or mutated Catenin)
2) Degradation of basement membrane and E.C. matrix (MMPs)
3) Attachment of tumor cells to exposed basement membrane components (mediated by laminin & fibronectin receptors)
4) Migration of escaped malignant tumors through interstitium (autocrine motility factor)
What is the metastatic trend for colon cancer (where does it travel)?
Colon –> Lymph nodes –> liver
Where do prostate and breast cancers normally metastasize to?
breast/prostate–> lymph nodes –> bone
Why do cancers have normal metastatic pathways?
Combination of drainage pathway and organ differences (some organs have different endothelial cell ligands expressed for adhesion molecules, etc)
Where can tumor cells travel when they invade veins and what life-threatening condition can they cause?
- Pass through right heart and go to lungs
- Tumor embolus gets stuck and clot formation obstructs small pulmonary blood vessels
- leads to pulmonary hypertension and right heart failure
What does a carcinogenic initiator do?
Causes a pre-cancer mutation
What does a carcinogenic promoter do?
Causes proliferation of initiated cells
What’s an example of a direct chemical carcinogen?
Few examples, mainly reactive electrophiles
How do indirect chemical carcinogens function?
require metabolic activation of pro-carcinogen
-this is commonly done by CYP40 Monoxygenases
What are some examples of indirect chemical carcinogens?
Estrogen, alcohol, anti-cancer chemotherapy agents
How does obesity increase a patient’s risk for breast cancer?
Fat cells make estrogen, a pro-carcinogen
What can radiation therapy cause?
Sarcoma development
What type of cancer does nuclear power plant leaks commonly cause?
Thyroid cancer
What kinds of cancer does HPV cause?
Uterine cancer, cancers of the mouth and upper respiratory tract
What kind of cancer do Hep C and Hep B cause
Liver cancer
What cancer does Epstein Barr virus cause?
Lymphoma (in immunocompromised patients)
What cancers can Helicobactor pylori cause?
Lymphoma, gastric carcinoma
T/F Development of a vaccine against HPV has made it possible to prevent many cancers of the uterine cervix
True
What is the principle effector mechanism by which the immune system scans for tumors?
CD8 cytotoxic lymphocytes recognize tumor antigens
-NK cells, macrophages and antibodies also play a role
What are a few way in which tumor cells can resist immune surveillance?
Decreased expression of MHC molecules, lack of co-stimulation, antigen masking
- Tumors can also induce TGF beta, which is a potent immunosuppressant.
- tumor cells can activate Tregs to suppress immune response
- Some tumors express FasL which can engage Fas on immune cells and induce apoptosis in the immune cell
What is a paraneoplastic syndrome?
symptoms not attributable to direct effects of tumor are called paraneoplastic
-most common is hypercalcemia (due to release of parathyroid hormone-related protein from tumor)
What is Cachexia?
Catabolic state of severe wasting mediated by tumor necrosis factor
-cancer is the most common cause
What type of lung cancer most commonly causes hypercalcemia?
Squamous cell carcinoma
Is hypercalcemia a complication of malignancy?
Yes,
common symptoms are nausea, vomiting, altered mental status
What is a common cause of Cushing syndrome?
Pituitary adenomas
-overproduction of ACTH causes adrenals to constantly make cortisol. This causes weight gain, central obesity, moon face, weakness, hypertension…et al
T/F cancer causes a hypocoagulable state
False, cancer causes a hypERcoagulable state
What is tumor stage?
Anatomical extent of a tumor
- primary tumor size, extent of lymph node and distant metastases
- Radiologist thing
What’s tumor grade?
Qualitative assessment of tumor differentiation
- How bad does it look in comparison to normal tissue
- Pathologist thing
Does tumor stage or grade carry more weight in a prognosis?
Tumor stage carries far more prognosis than grade
