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180 Cards in this Set
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- Back
- 3rd side (hint)
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What are the basic components of all tumors?
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parenchyma and supportive stroma
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What is a neoplasm?
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abnormal mass whose growth exceeds that of normal tissue and continues after stimuli is gone
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Benign or malignant:
hemiangioma |
benign cancer of the blood vessel
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not angiosarcoma
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Benign or malignant:
rhabdomyoma |
benign cancer of striated muscle
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not rhabdomyosarcoma
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Benign or malignant:
leiomyoma |
benign cancer of smooth muscle
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not leiomyosarcoma
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Benign or malignant:
adenoma |
general term for benign tumor
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Benign or malignant:
mature teratoma |
benign totipotential cells
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immature teratomas are malignant
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Benign or malignant:
squamous cell papilloma |
benign epithelial lining cancer
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Benign or malignant:
lymphoma |
malignant lymphoid tissue cancer
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lymphomas and leukemias are malignant
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Benign or malignant:
leukemia |
malignant hematopoietic cells
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lymphomas and leukemias are malignant
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Benign or malignant:
liposarcoma |
malignant fat
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Benign or malignant:
melanoma |
malignant neuroectoderm
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Benign or malignant:
nevus |
benign neuroectorderm
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Benign or malignant:
seminoma |
MALIGNANT testicular epithelium
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Benign or malignant:
choristoma |
ectopic displacement of normal tissue
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heterotopia
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Benign or malignant:
hamartoma |
benign, mostly in lung;
indigenous tissue gone crazy. |
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What is notable about neoplastic cell nuclei, chromatin, etc?
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large nuclei with hyperchromasia
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What are the differences between benign and metastatic tumors?
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benign tumors are encapsulated, expansile and have a well-defined cleavage plane while malignant tumors have no regard for anything and just invade
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All cancers can metastasize except for what?
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gliomas and basal cell carcinomas
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What are the pathways of metastatic spread?
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body cavity seeding, lymphatic spread, or hematogenous spread.
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What are skip metastasis?
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local lymph nodes that are bypassed by malignant cells because of venous-lymph anastamoses or because of obliterated channels (due to inflammation)
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What does enlarged lymph node signify?
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either the spread and growth of cancer cells OR reactive hyperplasia (doesn't necessarily mean cancer has disseminated)
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What is a sarcoma?
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is a cancer of the connective tissue resulting in mesoderm proliferation
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What is a carcinoma?
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is any malignant cancer that arises from epithelial cells
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Which organs are most frequently involved with hematogenous dissemination?
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liver and lung; they filter all the blood
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Why is venous spread of cancer more common?
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arteries are thicker and less penetrable
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What is the death rate of those with cancer?
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1 in 5 die
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What is % of all mortality caused by cancer?
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25%
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Why has the death rate for men increased while the rate for women decrease?
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Men has more lung cancer, pap smear is used for women to decrease gynecological cancer
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What is soon to be the leading cause of death?
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Lung (followed by prostate/colonrectum for males and breast/colonrectum for females)
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What is the most common carcinomas in children?
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leukemia, brain, and endocrine
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Pattern of inheritance?
RB |
AD
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Pattern of inheritance?
FAP |
AD
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Pattern of inheritance?
MEN |
AD
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multiple endocrine neoplasia syndromes
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Pattern of inheritance?
xeroderma pigmentosum |
AR
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Pattern of inheritance?
ataxia-telangiectasia |
AR
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Pattern of inheritance?
Bloom syndrome |
AR
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Pattern of inheritance?
Fanconi anemia |
AR
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What characterizes familiar cancers?
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- early age of onset
- multiple bilateral tumors - no specific marker phenotype - TUMORS ARISING IN TWO OR MORE CLOSE RELATIVES |
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What kind of a cancer or transmission pattern is BRCA1 and BRCA2?
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it is a familiar cancer with unclear transmission pattern for breast and ovarian cancers
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How common are hereditary cancers?
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5-10% of all cancers
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How do polymorphisms contribute to cancer?
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Certain genotypes determine disposition of cancer susceptibility to carcinogens.
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What cancer does asbestos cause?
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Lung, GI, mesothelioma
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What cancer does vinyl chloride cause?
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Angiosarcoma of the liver
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What cancer does most metals cause?
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Lung (nickel, chromium)
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What cancer does cadmium cause?
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prostate
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What cancer is fungal metabolite carginogens associated with?
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liver
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What light spectrum is responsible for skin cancers?
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UVB (280-320 nm)
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What about UVB causes cancer?
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it forms pyrimidine dimers in the DNA which has the potential to overwhelm the NER repair pathway
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What are the most frequent cancers due to ionizing radiation?
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leukemias (think the a-bomb)
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What disease can never follow radiation injury?
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chronic lymphocyte leukemia (CLL)
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What are the DNA oncogenic viruses?
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HPV, HBV, EBV, and KSHV
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Kaposi's sarcoma-associated herpesvirus in AIDS or immunocompromised pts
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What is HTLV-1?
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an RNA oncogenic virus: human T-cell Leukemia Virust Type 1 and is a STD
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What cancer does H. Pylori cause and how?
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It causes B-cell lymphoma because T-cells activated by the bacteria stimulates monoclonal B Cell proliferation
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Treatment with antibiotics remove the antigenic stimulus for T cells and therefore chemical signals for B cell proliferation
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What can HPV cause?
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squalous papillomas, squamous cell carcinoma, oral/laryngeal cancer
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Which are the LOW risk types of HPV?
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HPV 6 and 11
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6:11
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What must occur for HPV to be cancerous?
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It must be integrated into the host cell genome
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Where does HPV insert itself in the host genome?
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E1/E2 open reading frame
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What are the gene products of HPV and what do they do?
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proteins E6 and E7 which bind to p53 and underphosphorylated RB to cause major disregulation of cell cycle.
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Why are HPV 16 and 18 more high risk?
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Their E6/E7 protein products have a higher affinity to p53 and unphosphorylated RB than lower risk types
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What cancers are caused by EBV?
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Burkitt's lymphoma, B-cell lymphomas, Hodgkin's and nasopharyngeal carcinomas
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BBHN
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How does HBV enter cells?
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via CD21
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What is LMP-1 and what does it do?
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It is latent membrane protein-1 of EBV which mimicks the action of CD40 to receive T-cell signals
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What is a neoplasm of B-lymphocytes whose initator is EBV? What gene is dysregulated?
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Burkitt's lymphoma; disregulation of c-MYC oncogene
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most common childhood tumor in central Africa and New Guinea
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What is present in 100% of nasopharyngeal carcinoma patients?
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EBV
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How does HBV cause HCC?
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insertional mutagenesis to cause regernative hyperplasia and interference with growth control (HBx protein)
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What is HTLV-1 similar to?
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AIDS because of tropism for CD4_ t-cells
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What STD contains gag, pol, env, and LTR regions?
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HTLV-1
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What genes and mediators are essential for viral replication of HTLV-1?
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TAX, IL-2, and M-GMSCF
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What is the sequence of disease states once infected by H. Pylori?
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chronic gastritis, multifocal atropy, metaplasia, dysplasia, carcinoma
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GAMDC
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What does H. pylori with CagA cause?
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with the cytotoxin associated gene A, H Pylori causes ulcers.
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What carcinoma famously has signet rings?
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Gastric carcinomas.
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What size is the tumor with smallest detectable mass?
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30 doublings or 10^9 cells
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What is the largest tumor size compatable with life?
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10^12
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What is the rate of growth of a tumor determined by?
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doubling time, growth fraction, production vs loss
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What part of tumor kinetics is susceptible to chemotherapy?
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growth fraction
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What normal genes are the principal targets of genetic damage?
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proto-oncogenes
grwoth inhibiting tumor suppressor genes apoptotic genes DNA repair genes |
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AD mutations of which kinds of normal genes result in cancer because only one allele needs to malfunction for dysregulation?
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oncogenes because mutation leads to some growth promoting activities
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AR mutations of which kinds of normal genes result in cancer because suppression/inhibition can occur with one functioning allele?
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tumor suppressor genes and DNA repair genes. EXCEPTION: haploinsufficiency, then there is no normal allele
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What is essential for tumor malignant transformation?
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self-sufficiency in growth signals, desensitivity to inhibitory signals, evasion of apoptosis, DNA repair defects, limitless replicative potential, and sustained angiogenesis and ability to metastasize
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What protein family products are essential for cell cycle regulation?
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Cyclins, cyclin-dependent kinases, and inhibitors
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What cell cycle regulatory protein is constitutively expressed but usually in inactive form?
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CDK's which are activated by phosphorylation
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Which cell cycle protein is synthesized at specific stages of the cell cycle and in what order?
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Cyclins DEAB
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What cell protein complex phosphorylates the RB protein?
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CyclinD-CDK-4
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Where are the checkpoints of the cell cycle?
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between G1/s and G2/M
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What is the role of the cell-cycle inhibitor p21?
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to mediate the G1/S checkpoint through p53
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How do tumor cells bypass apoptosis?
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they pybass the checkpoints to avoid apoptosis
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What are oncogenes?
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cancer causing genes due to mutation of protooncogenes (genes that control production of GFs, GF receptors, signal transduction, regulatory proteins, cell-cycle regulators, suppressors of apoptosis)
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What does the RET protoncogene associate with?
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MEN, familial thyroid carcinoma, and Hirschprung disease
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Overexpression of EGFR causes what?
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overexpression of this protooncogene causes lung tumors, glioblastomas, head/neck tumors
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What is overexpressed in breast cancer?
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the ERB-B2 HER-2/NEU protooncogenes
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What can be targeted in GI stromal cancers?
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receptor TK activity of c-kit
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What can be used against overexpression of HER-2/NEU?
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herceptin, Ab's against the gene that causes breast tumors
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What are the two main classes of CDK inhibitors?
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Cip/Kip and INK4/ARF
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Dog named ___ that goes ____!
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Cancer associated with RAS
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pancreatic adenocarcinomas
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Cancer associated with KRAS
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carcinomas
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Cancer associated with HRAS
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bladder tumor
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Cancer associated with NRAS
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hematopoietic neoplasms
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Codons most commonly involved with RAS mutations.
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12, 59, 61
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What is the therapy for chronic myeloid leukemia (CML)?
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imatinib mesylate
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highly effective targeted therapy
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The MYC oncogene is overexpressed in what cancers?
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breast, colon, lung carcinomas
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The N-MYC oncogene are amplified in what cancer?
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neuroblastoma
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Cancer associated with mutation of: WT-1
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Wilms tumor on Ch11
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Cancer associated with mutation of: VHL
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clear cell renal carcinoma
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von Hippel Lindau
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Cancer associated with mutation of: RB
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retinoblastoma or osteosarcoma
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Cancer associated with mutation of: p53
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Li-Fraumeni syndrome
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Cancer associated with mutation of: APC
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adenomatous polyps (dragon colon)
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Cancer associated with mutation of: B-catenin
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colon cancer
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Cancer associated with mutation of: INK4a/ARF
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familial melanoma
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Cancer associated with mutation of: TGF-B
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colonic carcinoma in patients with HNPCC
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Cancer associated with mutation of: NF-1
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neurofibromatosis type 1 -- this is a GTPase-activating protein
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Cancer associated with mutation of: NF-2
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neurofibromatosis type 2 -- this is MERLIN protein which forms cell-cell junctions
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Cancer associated with mutation of: WT-2
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Beckwith-Wiedmann
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Cancer associated with mutation of: DCC
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Ch18q21 in colon and renal carcinoma
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Cancer associated with mutation of: cadherin proteins
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breast, esophagus, colon, ovarian cancer
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What is the two hit hypothesis?
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One hit is hereditary, the second mutation happens in a cell with the first mutation so both alleles are mutated.
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in tumor suppressor genes
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What is the antiapoptotic gene?
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BCL
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What does p53 increase the expression of?
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BAX, a gene promoting apoptosis
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What causes increased genomic instability?
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defective DNA repair genes
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What are the important DNA repair systems?
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Nucleotide excision
Mismatch Repair Recombination |
NMR
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What is the hallmark of defective mismatch repair?
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microsatellite instability
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What is xeroderma pigmentosum?
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AR, defect of the NER pathway
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What is a metastasis signature?
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the combination of genes involved in metastasis
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What protein products are vital for metastasis?
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fibronectin and lamini for adhesion/motility
metalloproteinases to degrade ECM |
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What does CD44 do?
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adheres the tumor to endothelium
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What is NM23?
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gene that suppresses metastasis genes
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What is aneuploidy?
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changes in chromosome number
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What gene is translocated in CML?
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chronic myeloid leukemia - the ABL gene
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What gene is translocated in Burkitt's lymphoma
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C-MYC
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By what mechanism of mutation does Ewing's Tumor arise from?
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fusion genes by reciprocal translocation
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What is overexpressed in neuroblastomas?
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N-MYC
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What is overexpressed in breast cancer
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ERB B2
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Aside from mutations, how can tumor suppressor genes be inactivated?
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hypermethylation
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What are gatekeeper genes?
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oncogenes and tumor suppressor genes
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What are caretaker genes?
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genes that control genomic stability like DNA repair genes
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Do gatekeeper genes or caretaker gene mutations increase risk for malignancy?
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Gatekeeper genes have a higher risk of developing malignancies.
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What is microarray technology?
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large scale analysis of gene expression
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What can be used to avoid contamination of tumor sample with surrounding structures?
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laser capture microdissection
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In proteomics, how are protein samples separated?
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by mass and charge
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What is the concept of immunosurveillance?
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The idea that a major function of the immune system is to control cancer development
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What is the concept of immunoeditin?
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The idea that immune system prevents tumor formation but also selects for tumor variants that escape immune elimination
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What are tumor specific and tumor associated antigens?
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Tumor specific antigens are present only on tumor cells while tumor associated antigen are also found on normal cells
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What are the main classes of tumor antigens?
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Products of oncogenes and mutated tumor suppressor genes, overly expressed cellular proteins, antigens produced by oncogenic viruses
oncofetal, altered surface, and cell specific differentiation antigens |
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What tumor antigen type is important for development of cancer vaccines?
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surface glycolipids and glycoproteins
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What tumor antigen type is important for immunotherapy and identification of tissue of origin?
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Cell-type specific differentiation antigens
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What is the main mechanism of tumor immunity?
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mell-mediated CD8+ killer T
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What are the main effectors for killin tumors?
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Killer T, NK, Macrophages, ADCC (type IV)
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What are the common mechanisms that tumors use to escapt the immune system?
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Selective growth of antigen negative varients
loss of MHC loss of co-stimulations Immunosuppressive tumor products |
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What is TGF-B?
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immunosuppressive product made by tumor cells to escape immune surveillance
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What are two arguments against immune surveillance?
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immunodeficient hosts get lymphomas and also the immune system helps tumors grow with their secretions
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What is cancer cachexia?
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increased metabolic rate, equal fat and muscle loss
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What is the mechanism for cancer cachexia?
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TNF, IL-1, IFN-a
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cytokines secreted by host macrophages/tumor cells
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What mysterious condition occurs in 10% of patients with malignancies?
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paraneoplastic syndromes
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What is the most common endocrinopathy?
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Cushing's syndrome
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What do 50% of patients with paraneoplastic Cushing's syndrome have?
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small cell lung cancer
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What is the most common paraneoplastic syndrome?
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hypercalcemia
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What is the most common lung cancer associated with hypercalcemia?
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squamous cell bronchogenic carcinoma
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What is seen in 1-10% of patients with bronchogenic carcinoma?
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Hypertrophic osteoarthropath
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What syndrome is associated with pancreatic.lung cancers?
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Trousseau's sign.
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Acute disseminated intravascular coagulation is a paraneoplastic syndrome most commonly found in what cancers?
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acute promyelocytic leukemia and prostate cancer.
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increased coagulation factor synthesis
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What is thrombotic endocarditis and what cancers are they associated with?
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it is the deposition of small sterile vegetations on valve leaflets associated with mucin secreting adenocarcinomas
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How are tumors graded and staged?
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Grading = level of differentiation; Staging = size, lymph nodes, and metastatic presence
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TNM
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What is the scale for primary tumor sizing?
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T1-4
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What is the scale for nodal involvement?
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N 0-3
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What is the scale for metastasis?
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M 0-2 (none, local, distal)
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Staging or grading: important for therapeutic management
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staging (it is more prognostic)
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Staging or grading: more important.
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Staging
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What histologic method is used for superficial, palpable lesions?
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Fine needle aspiration
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What biopsy method is used for larger samples?
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Needle core biopsy
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What is the last resport biopsy method for diagnosis of cancer?
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excisional biopsy
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What disease is the following associated with: CEA
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colon cancer
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What disease is the following associated with: AFP
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HCC
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What disease is the following associated with: PSA
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prostate cancer
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What disease is the following associated with: CA125
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ovarian tumors
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What are the psychological effects of cancer?
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Denial, Anger, Bargaining, Depression, Acceptance
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In what cancer do most muscular and neuro paraneoplastic degenrations occur?
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small cell lung cancer
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What paraneoplastic syndrome occurs often with intra-abdominal malignancies?
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acanthosis nigricans
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In what cancers might polycythemia occur?
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Renal, cerebellar, Liver
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What is carcinoid syndrome?
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flushing, diarrhea
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What mediates carcinoid syndrome?
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histamine, serotonin, bradykinin to cause flushing, redness of the skin and pain.
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