Neoplasia II - Nichols Flashcards
What is cachexia?
catabolic state of severe wasting mediated by TNF. Commonly caused by cancer, AIDS, end-stage heart disease and end-stage lung disease.
What are paraneoplastic syndromes?
symptoms not attributable to the direct effects of tumors. Occur in about 10% of cancer patients. Cachexia is not counted as one since it is present in nearly 100% of cancers.
Describe the grades of tumors.
rating based off microscopic appearance of tumor cells. Generally the more undifferentiated it is, the higher the grade
Describe the stages of tumors.
Cancer staging takes into account tumor size and invasiveness. Generally much more prognostic than grade.
Define cytology.
sample of cells exfoliated or aspirated from the body
How do BRCA gene mutations lead to early breast cancer?
The are believed to function in a common DNA repair pathway.
How does t(14;18) translocation lead to follicular lymphoma?
almost 85% of follicular B-cell lymphomas have this mutation. The t(14;18) translocation fuses BCL2 gene from chromosome 18 with the active IgH locus on chromosome 14, resulting in overproduction of anti-apoptotic BCL2. This decrease in apoptosis, combined with the already long life of B cells, causes a slow accumulation of excess lymphocytes over many years, enlarging the lymph nodes around 60 years of age. Usually the best treatment is no treatment.
Describe the mechanism of sustained angiogenesis.
Normally angiogenesis is inhibited by thrombospondin-1 (induced by p53) and destruction of HIF-1 by VHL. When these mechanisms are knocked out, VEGF and PDGEF cause unregulated growth of irregular leaky blood vessels.
Why is bevacizumab limited in its efficacy as an anti-cancer drug?
bevacizumab is an anti-VEGF agent that prevents neoangiogenesis. It is not as efficacious as was hoped becuase cacners smaller than 2 mm can survive without angiogenesis and a large number of them can still have a lethal effect. This does decrease large tumors effectively though.
What are the 4 stages and mechanisms of tumor invasion
- detachment of tumor cells from each other. (mediated by down regulation of E-cadherin or mutated catenin)
- degradation of basement membrane and extracellular matrix (performed by MMPs)
- attachment of tumor cells to basement membrane (laminin and fibronectin receptors mediate)
- migration of the escaped malignant cells through the interstitium (mediated by binding to factors such as autocrine motility factors)
What is the difference between tumor metastasis and tumor embolus?
tumor ebolus is when tumor cells invade veins elicit formation of blood clot around them and fibroblasts then organize it.
Tumor metastasis is just the process of invasion and movement to a new area.
What are the essential features of radiation carcinogenesis?
It has a long latent period (years-decades). UV radiation can cause skin cancer, whereas radiation therapy can cause sarcomas. Nuclear power plant leaks can cause thyroid cancers.
What is anti-tumor surveilance? How does it work? How do tumors evade it?
Immune system provides some defense against tumors by recognizing tumor antigens. Principal mechanism is by CD8+ cytotoxic T cells. NK cells, macros and antibodies also help. Tumors can resist this though by outgrowth of Ag-negative cells and decreased expression of MHC. They can also induce TGF-beta, which is a potent immunosuppressant, or express FasL, which will engage Fas on immune cells and induce apoptosis in them.
What are the major direct effects of tumors?
they can impinge on adjacent structures, cause obstruction, secrete hormones, cause ulceration, bleeding, infection, infarctions, ruptures, or cause ischemia in adjacent structures or tissues.
What are the 3 major paraneoplastic syndromes?
hypercalcemia, Cushing syndrome, carcinoid syndrome
What is paraneoplastic hypercalcemia?
When hypercalcemia is caused by parathyroid hormone-related protein (PTHRP) and other substances released by tumors.
Symptoms include nausea, vomiting, constipation, polyuria, disorientation, lethargy and seizures. Treat with hydration and bisphosphonates.
What is Cushing syndrome?
due to tumor ACTH production. Can be paraneoplastic. Most commonly caused by pituitary adenomas or small cell carcinoma of lungs. Symptoms of weight gain, central obesity, moon face (fat deposition), weakness, hirsutism, hypertension, glucose intolerance, depression, psychosis, broad red abdominal striae, buffalo hump dorsal neck fat deposition, plethora, osteoporosis, menstrual irregularity, muscle wasting.
What is carcinoid syndrome?
due to serotonin released by tumors
What is the difference between tumor stage and grade?
Tumor stage is the anatomic extent of tumor, including primary size, extent of lymph node and distant metastases.
Tumor grade is qualitative assesment of the differentiation of a tumor (microscopic appearance). It is mostly a radiologic and pathologist thing.
Usually stage carries more prognosis than grade.
