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95 Cards in this Set
- Front
- Back
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What is the classification of neoplasms primarily based on?
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Presumed cell of origin
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What kind of cell is the origin of a carcinoma?
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Epithelial
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What kind of cell is the origin of a sarcoma?
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Mesenchymal
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What kind of cell is the origin of a leukemia?
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Hematopoietic
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What kind of cell is the origin of a lymphoma?
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Lymphoid tissue
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Is a teratoma malignant or benign?
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Benign
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Is a melanoma malignant or benign?
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Malignant (exception to the nomenclature rule)
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Is a hepatoma malignant or benign?
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Malignant (exception to the nomenclature rule)
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What is a hamartoma?
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A disorganized mass of cells in the right place but put together wrong (some are benign, some are malignant)
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What is the name for a benign neoplasm of fat? For a malignancy of fat?
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Lipoma
Liposarcoma |
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What is anaplasia?
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Less differentiation than normal - this is a characteristic of malignant neoplasms
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What are some characteristics of benign neoplasms?
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Almost always well-differentiated
Slow-growing Scant mitoses Encapsulated and pushing margins Localized |
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What are some characteristics of malignant neoplasms?
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Anaplasia
Loss of polarity and cohesion Large nuclear:cytoplasmic ratio, hyperchromatic nuclei with clumping of chromatin and a big nucleolus |
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What does the grade of a tumor represent?
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The degree of anaplasia present
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What are three conditions/places where dysplasia is commonly encountered?
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Cervix, Barret's esophagus, ulcerative colitis (it is usually in epithelia)
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What are three cancers with high rates of malignancy by the time a diagnosis has been made?
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Lung (76%)
Colorectal (55%) Breast (37%) |
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What are two types of malignancies that almost never metastasize?
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Basal cell carcinoma of skin
Gliomas |
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What is the typical route of metastasis of sarcomas? Of carcinomas?
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Sarcomas spread by blood (although they can spread via lymphatics)
Carcinomas spread by lymph |
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What is the single most important predictor of prognosis in malignancy?
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The stage (denoted by extent of spread)
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What are two very common sites of hematogenous metastasis?
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Liver and lung
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What are the four main gene targets in neoplastic transformation?
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Proto-oncogenes
Suppressor genes Genes controlling apoptosis DNA repair genes |
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What are four possible causes of genomic instability seen in malignant transformation?
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Loss of DNA repair mechanisms
Mutations in genes controlling mitosis Hypomethylation of DNA Bridge-fusion-breakage |
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What do experts think the role of aneuploidy is in transformation?
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Significant when it is there but overall, it plays a minor role
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When do proto-oncogenes become oncogenic?
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When the gene or its product is either mutated, affected by other genes through regulatory pathways, loses activity of miRNAs, or is acted on by viral proteins
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What is HER-2?
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A gene that codes for a growth factor receptor that becomes oncogenic when amplified and may lead to breast cancer (in these patients, trastuzumab which is a MC-AB therapy may work)
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What gene is most often abnormal in oncogenes of human tumors?
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RAS (15-20% of human tumors have mutated RAS)
-90% in pancreas and bile duct -50% in colon, endometrium, and thyroid -30% in lung and myeloid leukemia |
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Why is it important to identify whether a RAS mutation is present in metastatic colon cancer?
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Because if it is, then monoclonal antibody therapy that works at the EGF receptor (cetuximab or panitumumab) will not work
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What types of genes are all known to be altered in cancer?
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Early response genes of signal transduction pathways
Close to 70% of malignancies show dysregulation of MYC (persistent and/or over-expression) |
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What must MYC dimerize with the be activated?
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MAX (MAD competes with MYC for MAX)
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What do MYC/MAX dimers accomplish?
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Bind to E-box to drive transcription --- effect chromatin structure and gene expression
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What to MAD/MAX dimers accomplish?
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Repress transcription
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What is the normal chomosome for the abl gene and where does it get translocated in CML?
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9 --> 22
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What happens in Burkitt's lymphoma?
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MYC gene translocates from chromosome 8 to chromosome 14
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What are some of the effects of the myc protein?
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Integrates information from various signal transduction pathways so diverse:
-Enhancement of progression into G1 -Promotion of angiogenesis -Inhibition of differentiation -Increased genomic instability -Increased telomerase activity -Loss of E-cadherin expression |
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What are two proteins that, when acting inappropriately, enhance the oncogenic potential of myc?
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RAS (increases MYC half-life)
BCL (inhibits apoptosis) |
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How does the carcinogenic role of tumor suppressor genes happen?
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Loss of activitiy
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What other neoplasms does the RB gene play a role in?
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People with familial retinoblastoma have increased risk of osteosarcoma and certain other sarcomas
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What does active RB look like?
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Binds E2F, histone deacetylase and histone methyltransferase -- makes a complex that does not lead to transcription because E2F is occupied
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What do growth factors do in the RB pathway?
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activates cyclin D/CDK4 which phosphorylates RB which causes the complex to break apart and E2F is freed to do transciption
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What is the feedback loop involving E2F1?
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it activates p14arf, which inhibits MDM2, stopping the inactivation of p53 and allowing p53 to activate p21 to inhibit cyclin D/CFK4's phosphorylation of RB
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What happens when too much E3F1 is activated?
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Apoptosis, via p14arf, p53, and p53-independent mechanisms
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What are four areas where neoplasms often have dysregulation related to RB?
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Mutation of RB at site of E2F binding
p16INK4A mutation, which takes away a Cyclin D/CDK4 brake Over-activation of cyclin D/CDK4 oncogenic DNA viruses binding to and resulting in a functional deletion in RB (inactivate p53 too) |
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What is the most common gene where there is alteration in human tumors?
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p53
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What is the main inhibitor of p53? What is the main inhibitor of that?
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MDM2
p14ARF |
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What are five possible outcomes of the p53 protein activation?
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growth arrest
DNA repair induction of apoptosis induction of senescence activation of MDM2 |
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What types of mutations are commonly seen in p53?
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>95% are point mutations
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What is the function of p14arf?
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safeguard against oncogenic stress (promotes p53, which has the power to repair or apoptose trouble cells)
it also directly inhibits MYC protein |
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What cells carry out the apoptosis instructed by p53?
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BAK/BAX make channels in mitochondrial membrane so that cytochrome c can leak out and lead to apoptosis (promoted by p53), BCL2 bind to the membrane preventing a pore from forming and is inhibited to allow this
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What happen in 85% of follicular B-cell lymphomas?
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14;18 translocation puts gene for BCL-2 into immunoglobulin heavy chain locus, making BCL-2 be overexpressed and counteracting any apoptotic signals sent by p53 due to damage or stress
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What would happen if MYC and BCL-2 were both other-activated?
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MYC would lead to proliferation, and BCL-2 would maintain the levels since it is anti-apoptotic
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What mechanism is defective in 15-17% of all colon carcinomas?
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DNA mismatch repair (3% have an inherited mutation, such as HNPCC)
Most with this are proximal to splenic flexure, poorly differentiated, large, lymph node negative, have a Crohn-like reaction, and are resistant to standard chemotherapy |
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What are three effects of neovascularization in tumor cells?
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Provides nutrients and oxygen
Endothelial cells secrete growth factors for the tumor cells New ways to do metastasis (higher the microvessel density in an area, the high the probability that it will metastasize) |
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What are some factors that promote angiogenesis in tumors?
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VEGF
bFGF hypoxia mutations in RAS, MYC |
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What are two signs to look for histologically when looking to see if the tumor has started local invasion?
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Altered matrix
Inflammation |
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What are the four steps of local invasion?
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1-Loosening of IC junctions (downregulation of E-cadherins, mutations in catenin
2-Tumors cells and/or stromal cells secrete proteases and metalloproteinase 9 to degrade basement membrane 3-Neoplastic cells bind to receptors for laminin and fibronectin using integrins 4-Migration into the stroma by contraction of actin in the tumor cell, receptors for ECM proteins, secretion of GFs with autocrine effects, and the cleavage products of collagen and laminin exerting chemotactic effects |
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What cells destroy circulating tumor cells?
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CD8 T cells and NK cells
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What are two tissues that are unresponsive to extravasation of metastasizing neoplastic cells?
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Spleen and skeletal muscle
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What percent of people with newly-diagnosed malignant non-skin neoplasms already have metastases?
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30-40%
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What are products of oncogenes or tumor suppressor genes that may be presented on MHC-Is of infected cells?
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Mutated RAS, BCR/ABL fusion proteins, or mutated p53 protein
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What does overexpression of c-erbB2 (her-2/neu) im ply?
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This happens in 30% of breast cancers and implies a worse prognosis but that MoAb therapy could be useful
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What are oncofetal antigens?
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Antigens expressed in embryonic tissues and cancer cells - if in an adult, a sign of cancer
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What is a oncofetal antigen associated with hepatocellular carcinomas and some gonadal germ cell neoplasms?
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AFP
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What oncofetal antigen is measured to monitor therapy of colon carcinoma?
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CEA
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What are two altered surface glycoproteins/glycolipids that may be able to be used to make a vaccine?
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MUC-1 (breast ductal carcinomas)
GM2 (melanomas) |
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What is a differentiation antigen expressed by normal and neoplastic cells that is found in B-cell lymphoma and used in MoAb therapy?
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CD20
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What is the most important effector cell in tumor immunity?
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CD8 T cell
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Name five occupation-related carcinogens that begin with "A" and the cancer associated with each.
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Arsenic --> skin/lung carcinomas
Aromatic hydrocarbons (soot, tar)--> skin/lung carcinomas Aromatic amines (benzidine, naphthylamine) --> bladder carcinoma Aflatoxin B1 (produced by Aspergillus on moldy grains/ntus) --> liver cell carcinoma Asbestos fibers (amphibole types) --> mesothelioma (pleura and peritoneum) and lung cancer |
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What are some drugs associated with increased risk for cancer?
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azathioprine, cyclosporine (immunosuppressants) --> lymphoma
chlorambucil, melphalan (alkylating agents) --> lymphoma, leukemia Cyclophosphamide (alkylating agent) --> bladder conjugated estrogens --> endometrium diethylstilbestrol (synthetic estrogen) --> vagina, cervix phenacetin-containing analgesics --> renal pelvis and ureter |
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What are two neoplastic conditions caused by chronic H. pylori?
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Gastric adenocarcinoma
B-cell lymphoma (MALTomas) |
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What types of HPV account for 70% of all cervical carcinomas?
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16, 18
5, 8, 14 assoc with skin carcinoma 30, 40 with carcinoma of larynx |
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What are the early gene products of HPV-16 and HPV-18? What do they inhibit?
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viral proteins E6 and E7, inhibit p53, p21, and RB-E2F so that growth is not arrested
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What are the two determinations for a malignant neoplasm?
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Grade: how differentiated the cells look under the microscope
Stage: how far have they spread from the original tumor site? (most valuable predictor of prognosis) |
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What are five essential metals?
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Zinc
Copper Iron Cobalt Calcium |
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What is wrist drop, colic, encephalopathy, gingival lines, and vasospasm symptoms of? (which metal poisoning)
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Lead
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Synthesis of what essential compound is impaired in lead poisoning?
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Heme
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If basophilic stippling on peripheral blood smear is seen poisoning by which two metals should be considered?
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Lead and arsenic
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What does cyclophosphamide do?
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cross-links guanine by alkylation
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What is the main side effect of cyclophosphamide?
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Hemorrhagic cystitis
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What does cisplatin/carboplatin do?
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crosslinks DNA with guanines, complexed with platinum
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What is the main side effect of cisplatin/carboplatin?
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nephrotoxic
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What does 6-mercaptopurine do?
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It is a purine analogue that inhibits enzymes in ribonucleotide synthesis (AMP)
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What enzyme is inhibited by methotrexate? What does this eliminate the production of?
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dihydrofolate reductase
dTMP |
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What is the side effect of methotrexate?
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hepatic fibrosis and cirrhosis
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The effects of what drug can be rescued with Leukovorin?
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methotrexate
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What enzyme is inhibited by 5-flurouracil?
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thymidylate synthase, which does dUMP-->dTMP
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What is the mechanism of action of doxorubicin?
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Inhibits topoisomerase II, intercalates between bps in DNA, causes double-strand breaks
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What is the harmful side effect of doxorubicin?
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can cause congestive heart failure
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What does etoposide do?
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inhibits topoisomerase and causes DNA strand breaks
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What does bleomycin do?
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intercalates into a DNA strand, complexes with iron, produces ROS
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What is a benefit of bleomycin?
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It is not immunosuppressive so is good for combination therapy
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What is a side effect of bleomycin use?
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Can lead to pulmonary fibrosis
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What is the mechanism of action of vincristine?
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inhibits microtubule polymerization (lengthening)
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What is a side effect of vincristine?
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Causes peripheral neuropathy
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What is a benefit of vincristine?
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Is not immunosuppressive so can be used in combination therapy
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What are two anti-neoplastic drugs that can be used in combination therapy because they are not immunosuppressive?
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Vincristine and Bleomycin
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