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50 Cards in this Set
- Front
- Back
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growth fraction is...
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cell proliferation/cell loss
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What determines whether a tumor will have a fibrous capsule?
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rate of growth. Slower growing malignant tumors and benign tumors generally have fibrous capsule.
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Routes of metastases
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direct seeding of body cavities - peritoneal implants of ovarian carcinoma
via lymphatics - carcinoma > sarcoma, follows pattern of lymph drainage via blood vessels carcinoma < sarcoma, follows pattern of venous drainage and frequently hits liver or lung because veins are easier to travel through |
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Describe dominant/recessive in targets of genetic damage
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protooncogenes are dominant
tumor suppressors are recessive apoptotic regulators can be either DNA repair are usually recessive Note: recessive genes can display dominance on pedigree. |
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What is RAS?
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It is an oncogenic g-protein. When the GTPase activity that inactivates the G protein dysfunctions and no longer occurs thereby constitutively stimulating cell division. Important for NF-1
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What is ABL?
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a gene important for Chronic Myelogenous Leukemia(CML)
a gene commonly mutated by 9:22 translocation that causes a hybrid gene to make a protein with a potent tyrosine kinase that sends growth promoting signals to nucleus |
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What is Myc?
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oncogene at nuclear transcription level. MYC protein binds DNA and activates transcription of growth related genes.
When Myc gene is translocated it gets overexpressed which causes overgrowth. |
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Oncogenes at cell cycle level?
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cyclin overexpression which allows easier traversal of checkpoints. CDKs can also be overexpressed to cause the same thing
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What is the mechanism of RB?
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It is a tumor suppressor gene that when dephosphorylated it binds to a transcription factor and inhibiting transcription(active). When it is phosphorylated, it releases E2F and allows it to promote transcription(inactive).
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What is the mechanism of p53
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p53 is a TSG.
p53 levels increase in response to DNA damage and induce p21 which encodes CDK inhibitor thereby halting G1 to S. P53 also induces GADD45 which is a DNA repair enzyme and if repair is successful MDM2 is expressed and degrades P53. If not, p53 engages apoptosis. Most common target for genetic aberrations in neoplasms. |
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Apoptotic genes
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frequently 3 letters starting with B.
BCL 2 is anti-apoptotic. Translocation from 18 to 14 causes overexpression which promotes cell proliferation. Pathway involves MYC and p53 genes. |
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DNA repair genes
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HNPCC is poster child for mismatch repair gene dysfunction and has genetic heterogeneity. Also one of the few autosomal dominant pre-cancerous conditions.
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What does microsatellite instability indicate?
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a dysfunction in a mismatch repair gene
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Xeroderma Pigmentosum
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Nucleotide Excision repair dysfunction that has genetic heterogeity.
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Dysplasia encompasses what features...?
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this is a characteristic of neoplasia.
pleomorphism(irregular cell shapes), nuclear abnormalities(high nuclear/cytoplasm ratio, nucleoli), mitotic figures, loss of polarity |
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anaplasia
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characteristic of neoplasia...
tumor giant cells and necrosis. severe form of dysplasia. |
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What new characteristics can neoplastic cells attain?
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neoantigens, oncofetal antigens, ectopic hormone production
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Discuss tumor growth.
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After 20 doublings, it is at 1 mg and needs new blood supply. At 30 doublings it is at 1 gram and is the limit of clinical detection. At 40 doublings, it is at 1 kg and you are dead.
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Tumor growth generalization
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malignant growth faster than benign growth. Poorly differentiated growth faster that well differentiated growth. Growth rate not constant and influences by many factors.
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Development of sustained angiogenesis
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needed at 1 mg or more. Balance of activators and inhibitors of angiogenesis. Vessels have abnormal pattern of growth and are leakier
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Invasion
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detach from neighbors, penetrate basement membrane and stimulate movement through membrane. Before penetration of basement membrane, it is called carcinoma in situ. After it is carcinoma.
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Common metastatic sites
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lymph node, liver, lung, bone, brain
uncommon: spleen, heart, striated muscle |
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What translocation is in Burkitt lymphoma?
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t(8:P14). This changes the regulatory mechanism for the MYC gene causing it to be overexpressed. (doesn't change actual protein like in CML)
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What methods usually turn protooncogene to oncogene
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translocation and gene amplification(homogenous staining regions or double minutes)
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What are common mechanisms to inactivate TSG?
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deletions and epigenetic changes.
Epigenetic changes are when you alter methylation of promotor sequences(not actual mutation) |
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miRNAs and cancer
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miRNAs do not code protein. primary mRNA is cleaved to make pre-mRNA where it interacts with a protein in cytoplasm called dicer that makes it into miRNA. miRNA interacts with RISC to silence a gene.
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Chemical carcinogens
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Initiators cause mutation. There are direct(carcinogens) and indirect(procarcinogens). Direct causes mutation, but indirect does not but your body turns it into something that does.
Promoters (cocarcinogens) simulate cell proliferation |
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Carcinogenesis requires...
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initiator and then a promoter
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Ames test
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tells you if a chemical is a mutagen(not carcinogen). Tests for both direct and indirect because it has added mammalian metabolic activating system(p450)
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Ionizing radiation causes damage by....
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NOT by affecting DNA. Rather it turns water into free radicals which then go on to damage DNA.
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HPV mechanism of carcinogenesis
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inhibits p53 function which inhibits growth arrest and apoptosis
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What causes this?
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These are benign HPV neoplasms.
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What are these?
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These are uterine-cervix, recto-anal squamous cell carcinoma. These are malignant neoplasms of HPV.
Histologically there is the classic keratin pearls on the right. Reserved for well differentiated squamous cell carcinoma. |
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What is this a classic example of?
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Burkitt Lymphoma(malignant neoplasm) caused by EBV. Note morphology is "starry sky". The sky is malignant lymphocytes. The stars are tingible body macrophages which is a macrophage that has apoptotic debris in cytoplasm.
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What neoplasms associated with EBV?
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Burkitt Lymphoma, B-cell lymphoma, hodgkin disease, nasopharyngeal carcinoma
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What is the mechanism by which EBV causes cancer?
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It enters via CD21, viral LMP-1 mimics CD-40 which stimulates proliferation/survival.
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What is this?
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A slide showing hodgkin disease you have a malignant cell called a reed-sternburg cell with very prominent nucleoli that is binucleated. This is a diagnostic cell for Hodkins disease usually caused by EBV. Sometimes can overlap with CMV.
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What is this?
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Nasopharyngeal carcinoma caused by EBV. Note how cells are bigger in the middle? Those are cancer cells mixed with lymphocytes.
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Hepatitis B Virus
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Probably promotor effect for hepatocellular carcinoma through indirect effect(cell death, increased cell division).
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What is this caused by? What is it?
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it is hepatocellular carcinoma.
caused by Hepatitis B Virus(DNA) or Hepatitis C Virus(RNA) |
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What is this? What causes it?
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Kaposi Sarcoma. Unclear mechanism of cancer causing. Malignant cells defining slit like spaces containing red blood cells.
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Human T-Cell leukemia Virus Type 1(HTLV-1)
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RNA virus(retrovirus). likes CD4 positive T cells that causes leukemia/lymphoma 40-60 years AFTER infection most likely with a promotor effect.
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What is this caused by?
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Human T-Cell leukemia Virus Type 1(HTLV-1)
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Helicobacter pylori
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gram negative bacillus that can cause gastric lymphoma/carcinoma via promotor effect.
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What is this caused by? WHat is it?
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Helicobacter Pylori. It is Gastric Carcinoma.
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Tumor immunity cells
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NK cells, CTL, activated macrophages, B cells
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Common neoplasms in immunocompromised patients
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lymphoma(EBV), Kaposi Sarcoma(KSHV), uterine cervical carcinoma(HPV), gastric carcinoma(Helicobacter pylori)
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breast cancer arises from....
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adenocarcinoma arises from ductal glandular epithelium
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Adenocarcinomas can generally be described as....
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scirrhous
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What is desmoplasia caused by in adenocarcinoma of the breast?
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the cancer cells stimulating the surround stroma to produce collagen.
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