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135 Cards in this Set
- Front
- Back
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What are the three most common tumors in men?
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1. prostate cancer
2. lung cancer 3. colorectal cancer |
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What are the three most common tumors in women?
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1. breast cancer
2. lung cancer 3. colorectal cancer |
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What are the three most frequent cancer death in men?
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1. Lung cancer
2. Colorectal cancer 3. Prostate cancer |
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What are the three most frequent cancer death in women?
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1. Lung cancer
2. Breast cancer 3. Colorectal cancer |
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Which of the following two cancer is antosomal dominant and which has defective DNA repair defect?
A. Familial adenomatous polyposis B. HNPCC C. Retinoblastoma D. Xeroderma pigmentosum |
Autosomal dominant: A, B, C
DNA repair defect: B, D |
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What are some features of familial cancers?
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1. early age onset
2. occurs in two or more close relatives 3. not associated with specific marker phenotypes. |
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Name some chronic inflamation conditions that may cause cancer.
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Ulcerative colitis
Crohn's disease H. pylori gastritis viral hepatitis Chronic pancreatitis |
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Name some precancerous conditions that are associated with cancer.
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Chronic atopic gastitis of pernicious anemia
Solar keratosis of skin Chronic ulcerative colitis Leukemia of oral cavity, vulva, and penis |
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What are the two nonhereditary predisposing conditions of cancer?
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1. Chronic inflammation
2. Precancerous conditions |
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Seven fundamental changes in cell physiology that together determine malignant phenotype.
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1. self-sufficiency in growth signals
2. insensitivity to growth-inhibitory signals 3. evasion of apoptosis 4. defects in DNA repair 5. limitless replicative potential 6. sustained angiogenesis 7. ability to invade and metastasize |
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What is the mode of protooncogen activation?
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insertional mutagenesis
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What type of protooncogene dose RAS belong to?
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Proteins involved in signal transduction
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What types protooncogenes are involved in self-sufficiency in growth signals of cancers?
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1. growth factors: SIS, TGF-α, HGF, HST-1, INT-2
2. growth factor receptors: Her2 (amplified in breast cancer), RET 3. signal transducing proteins: RAS, NF-1 4. Nonreceptor tyrosine kinase: ABL (except cABL) 5. transcription factors: MYC 6. cyclins and CDKs:cyclin D, CDK4 |
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List the sequential interactions between cyclins and CDKs that lead to G1-S progression.
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CyclinD:CDK4
E2F/DP1/RB CyclinE:CDK2 |
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Which cyclin:CDK complex is needed for G2-M progression?
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CyclinA:CDK2
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Which cyclin:CDK complex is needed for progression through M phase?
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CyclinB:CDK1
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Where is the site of action of p27?
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CyclinE:CDK2 downstream signaling
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CyclinE:CDK2 complex is later replaced by _____ in the absence of cyclin E.
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CyclinA:CDK1
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Where is the site of action of p21?
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CyclinD:CDK4 downstream signaling
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p21 is induced by ____ where as p27 is induced by ____.
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p53
TGF-β |
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Which two cell cycle inhibitors function at cyclinD:CDK4 complex?
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p21
INK4 |
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What is the funciton of MDM2?
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MDM2 is induced by successful DNA repair to inhibit p53, thereby resuming cell cycle.
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What are the mechanisms of growth factor activation in human tumors?
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1. mutation
2. gene rearrangement 3. overexpression |
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Describe the oncogenic version of the growth factor receptors.
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constituitive dimerization and activation without binding to the growth factor.
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What is the single most common abnormality of dominant oncogene in human tumors?
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Point mutations in Ras family gene.
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What is the normal signal pathway of Ras?
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Ras(GTP)/RAF/MAP
activation of transcription Regulators: GAP(GTPase activating protein): augment GTPase activity of Ras. NF-1: a GAP |
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Ras can indirectly regulate levels of cyclins. Explain.
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Ras->MAPK->AP-1 transcription factor.
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Give an example of nonreceptor tyrosine kinase alteration in tumor cells.
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Fusion of BCR-ABL gene-> myeloid leukemia.
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Which of the following is the most commonly involved trascription factor in human tumors?
A. MYB B. JUN C. MYC D. FOS |
C.
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Translocation of MYC and Ig gene results in ___.
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Burkitt lymphoma
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List some tumor suppressor genes.
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RB
p53 APC/β-catenin pathway INK4,ARF TGF-β NF-1,2 VHL,PTEN,WT-1,Cadherins,KLF6,PTCH |
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What is LOH?
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Loss of heterozygosity.
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Which is the first tumor supressor gene discovered?
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RB
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How does TGF-β induces inhibition of cellular proliferation?
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TGF-β induces p27 which blocks CyclinE/CDK2 signaling.
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What is a possible explaination of the pathogenesis of cervical cancer by HPV?
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HPV virus may alter tumor suppressor genes such as RB by E7 protein and p53 by E6 protein.
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Name some regulations of p53.
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1. incude P21, BAX (proapoptotic proteins which down regulates BCL-2)
2. induce GADD45 when DNA repair is successful. 3. GADD45 induces MDM2 which neutralizes p53 to resume cell cycle. 4. HPV E6 protein inhibit p53 |
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What is the action of cell cycle inhibitor ARF?
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Inhibit MDM2
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What is the normal APC/β-catenin pathway?
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without WNT:
APC causes degradation of β-catenin. With wnt: APC inactivated, β-catenin accumulates in cytoplasm, translocate to nucleus, induce transcription. |
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What is the importance of wnt?
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Major role in determining cell fate, adhesion, cell polarity during embryonic development. Also required for self-renewal of hematopoietic stem cells.
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Do HNPCC patients have normal levels of APC in the cytoplasms?
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Yes. But the β-catenin is altered, thus not susceptible to APC degradation.
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How do tumor cells evade apoptosis?
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lack of p53-> decrease in p21 and BAX-> lack of inhibition of Bcl2.
MYC collaborate by triggering proliferation while lack of p53 prohibits apoptosis. |
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How does defect in DNA repair contribute to tumor generation?
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Allow mutation to accumulate, leading to genomic instability.
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T/F: Microsatellite instability is the hallmark of defective mismatch repair.
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T. With errors in mismatch reapair, there are expansions and contractions of tandem repeats.
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Compare the defective DNA repair mechanism between HNPCC and Xeroderma Pigmentosum.
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HNPCC: defective mismatch repair.
Xeroderma Pigmentosum: defective nuclear excision repair (NER). |
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Give some examples of cancer associated with defective DNA repair by homologous recombination.
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BRCA1
BRCA2 ataxia-telangiectasia: ionization radiation. Defective ATM gene. Bloom syndrome: ionization radiation. fanconi anemia: DNA cross-linking agents. |
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What is the function of ATM gene that is mutated in ataxia-talengiectasia?
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ATM encodes a protein kinase that senses dsDNA breaks caused by ionizing radiation and oxygen free radical. The kinase also phosphorylates p53 which lead to cell cycle arrest in G1/S check point or apoptosis.
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What is the maximal size of the tumor without additional angiogenesis?
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1-2mm: the maximal distance across which O2 and nutrients can diffuse from blood vessels.
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How are tumor vessel different from normal blood vessels?
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tortous, irregular shaped
leaky due to VEGF continuous growth |
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What is angiogenic switch?
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the time when some cells in the tumnor change to an angiogenic phenotype.
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What are some angiogenic factors and what are some antiangiogenic molecules?
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angiogenic factor: VEGF, HIF-1
antiangiogenic molecules: thrombospondin-1(tumor cell), endostatin, tumstatin. |
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How does tumor cells invade ECM?
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1. detachment of tumor cells from each other: down regulation of E-cadherin which is linked to catenin.
2. attachment to ECM: via laminin, fibronectin, integrins receptors. 3. degradation of ECM: stromal cells produce matrix metalloproteinase(MMP2,9). 4. migration of tumor cells: cleave products serve as growth promoting, angiogenic, antiangiogenic(endostatin, tumstatin), and chemotactic activities. |
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How does tumor cells invade and metastasize?
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1. invasion of ECM
2. vascular dissemination and homing of tumor cells |
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After tumor cells invade ECM, how do they disseminate through blood and extravasate?
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1. tumor cells circulate in clumps
2. CD44 adhesion molecule facilitate adhesion to endothelial cells. Then tumor cells return to ECM through the same process it get out from it. |
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How are protooncogenes activated?
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1. translocation: remove protooncogenes from its regulatory elements, may also create fusion genes.
2. inversion |
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Translocation of cyclin D1 and IgH cause what type of cancer?
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Mantel cell lymphoma
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What is the genetic causes of chronic myeloid leukemia?
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translocation of BCR22 and ABL9 -> Philadelphia chromosome.
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How does epigenic changes contribute to carcinogensis?
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methylation of tumor-suppressor genes (ARF,INK, VHL...)
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What are some gatekeeper genes?
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oncogenes
tumor suppressor genes |
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What are some caretaker genes?
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DNA repair genes
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Describe tumor progression.
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Multiple mutations-> increase # of subclones (monoclone origin)-> more adept clones advances to cancer.
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What are the three types of carcinogenic agents?
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1. chemical
2. radiant energy 3. oncogenic virus and other microbes. |
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What is Her2?
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Protooncogene that codes for a growth factor receptor.
Becomes concogenic through amplification. Overexpressed om breast carcinomas. |
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Which gene is overexpressed in breast carcinoma?
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Her2
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What is cMYC?
How is it activated and regulated? |
1. growth response genes.
2. activated when MYC protein is dimerized with MAX protein. Mad competes for MAX, thus Mad:Max complex repress transcription. |
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What is the gene translocation in Burkitt lymphoma?
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MYC(Chromosome 8) and Ig(chromosome 14)
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What are some dysregulations of cMYC?
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1. alterations in signal pathway.
2. amplification: in neuroblastoma) 3. translocation: Burkitt lymphpma. |
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What are some effects of MYC protein?
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1. enhance progression into G1 phase.
2. promote angiogenesis 3. inhibit differentiation 4. increase chromosomal instability 5. increased telomerase activity 6. loss of E-cadhein expression. |
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What is the best combination for cancer progression (in tumor cells perspective)?
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MYC/Ras activation and anti-BCL protein expression.
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What is the one safeguard action of MYC protein?
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When it accumulates under oncogenic stress, it can trigger apoptosis.
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Explain the dominant negative mutation of p53 gene.
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p53 is a tetramer. Mutation in one subpart renders the tetramer defective.
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TGF-β upregulates ___ and favors active Rb protein.
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p27
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What is the most common site of genetic alteration in human tumors?
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p53
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What are some effects of acivated p53 protein?
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1. triggers p21
2. triggers GADD45: DNA repair 3. Bax: apoptosis 4. activate MDM2: feedback loop. |
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T/F: Loss of p53 or increased Bcl2 activity results in resistance to chemotherapy.
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True.
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How is MYC regulated?
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p14ARF directly inhibits it.
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What are the effects of p14ARF?
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1. inhibit MYC
2. activate p53 3. sensitize human cells to apoptosis: creating membrane pores. 4. inhibits proliferation by p53-independent pathway. |
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Is teratoma benign or malignant?
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benign
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Is melanoma benign or malignant?
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malignant
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Is Warth's tumor benign or malignant?
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malignant:papillary cystadenoma lymphomatosum.
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An ectopic rest of normal tissue is called ____.
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choristoma
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A disorganized mass of mature cells or tissue indigenous to the site is called ____.
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Hamartoma.
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Compare and contrast benign and malignant neoplasms.
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Benign: well differentiated, slow growing, mostly encapsulated, remain localized.
Malignant: anaplasia, rapid cell proliferation, almost never encapsulated, metastasize. |
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What are some cytologic changes of anaplasia?
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pleomorphism
increase in nucleus size tumor giant cell nuclear changes: enlargement, irregular shape, hyperchromatism, clumping of chromatin, increased number of mitoses, abnormal mitoses, large nucleoli. |
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What are some nuclear changes in anapasia?
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nuclear changes: enlargement, irregular shape, hyperchromatism, clumping of chromatin, increased number of mitoses, abnormal mitoses, large nucleoli.
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List some pathway of spread of malignant neoplasms.
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1. seeds cavities: pseudomyxoma peritonei
2. lymphatics: typical of carcinomas. 3. hematogenous: typical of sarcomas. |
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Do in situ malignancies metastasize?
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No.
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Why do people with HNPCC have better prognosis?
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DNA repair defect results in mutations in genes important for metastasis.
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T/F: Bcl dimers favor survival whereas Bax dimer favor apoptosis.
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T.
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A 14:18 translocation of Bcl-2 results in _____.
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follicular B cell lymphoma.
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How many doublings of tumor cells will result in 1gm, the smallest detectable tumor mass?
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30
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Describe the 4 steps of malignant neoplasm process.
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1. transformation
2. growth 3. local invasion 4. metastasis |
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Describe the process of local invasion.
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1. loosen IC junctions: down regulation of E-cadherin, mutations in catenin.
2. Attachment to ECM: increase integrin expression to bind to laminin and fibronectin. 3. degrade basement membrane: MMP2,9,serine, cysteine proteases. 4. migration to stroma: cleavage products have growth promoting, angiogenic, and chemotactic effects. Tumor cells develop receptors for ECM proteins and secrete growth factors with autocrine effects. |
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What blood cells helps metastasized cells survival and implantability on vascular epithelium?
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Platlets
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What are the key factor of tumor growth rate?
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1. doubling time
2. growth fraction 3. rate of cell death |
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How does debulking(surgery/radiation) help in tumor therapy?
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It shifts the remaining tumor cells from G0 to cell cycle, rendering it more susceptible to chemotherapy.
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Chemotherapy is most effective against ____ neoplasms.
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fast growing
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What happens when neoplasm has inadequate blood supply?
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hypoxia->apoptosis via p53
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What is the function of angiogenesis? (3)
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1. provide nutrients and O2
2. endothrlial cells secrete grwoth factors for tumor cells. 3. promote metastasis cia new vessels. |
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What are some angiogenic factors and anti-angiogenic factors?
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angiogenic factors: VEGF, FGF
anti-angiogenic factors: thrombospondin-1, angiostain(plasminogen cleavage product), tumstatin, endostatin(collagen cleavage product). |
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How do endostain and antibodies against VEGF fignt against cancer?
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by limiting angiogensis, causing lack of O2, nutrients for tumor growth.
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What are the most immune cells against tumors?
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CTL, NK cells
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What type of tumor antigens are there?
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1. proteins of mutated genes: p53, ras, CDK4, Bcl-Abl gene.
2. overexpressed antigens: c-erbB2(Her2) 3. viral antigens: E7 of HPV. 4. Oncofetal antigens: AFP, CEA can be used for diagnosis and monitor theapy. 5. differentiation antigen: CD10(B cell leukemia), PSA(prostate cancer) |
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What's the name of the mouse antibody that is used to target Her2 in breat cancer?
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trastuzumab
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What are some mechanisms that tumor cells use to escape immune system?
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1. outgrowth of antigen-negative variants
2. reduced expression of MHC class I molecules 3. cancer immunoediting: immune system selection of tumor subclones for survival 4. secretion of TGF-B for immune suppression 5. express Fas to induce apoptosis of CTLs |
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List some tumor effects on human hosts.
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1. local effects: ulceration of mucosa, obstruction of lumen, destruction of critical structures.
2. hormonal effects: pituitaty adenoma, islet cell cacinoma of pancreas, gastrinoma, carcinoid tumors. 3. cachexia: TNF-A effects. malaise, anorexia, weakness, wasting. 4. paraneoplastic syndrome |
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What are some tumor local effects on human hosts?
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ulceration of mucosa: adenocarcinoma of esophagus.
obstruction of lumen: colon carcinoma. destruction of critical structures: pituitary adenoma |
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What are some hormonal effects of tumor on human hosts?
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pituitaty adenoma: make prolactin, ACTH, GH
islet cell cacinoma of pancreas: secrete insulin, glucagon, somatostatin, vasoactive intestinal polypeptide. gastrinoma: produce gastrin. carcinoid tumors: neuroendocrine cells secrete serotonin, histamine, bradykinin, kallikrein, prostaglandins. |
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Which metabolite of serotonin cna be measured in urine, and is secreted in increased amount un carcinoid syndrome?
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5-HIAA
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What are the four symptoms of cachexia syndrome?
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malaise
anorexia weakness wasting |
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What do you suspect when a smoker comes in with Cushing's syndrome?
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Lung cancer
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Give two examples of paraneoplastic syndromes.
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1. Paraneoplastic Cushing syndromes: lung cancer (malignant neuroendocrine neoplasm). Weigh gain, central obeicity, moon facies, buffalo bump.
2. Acanthosis nigricans: gastic cancer. Thickened skin in axilla, oral mucosa involvement. |
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What is the most common cancer death in children?
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1. Acute leukemia
2. CNS malignancy |
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When should you start screen women for breast cancer?
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Start at age 40, annually thereafter.
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When should you start screen man for prostate cancer (PSA)?
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Start at age 50, annually thereafter.
*for African american or people with positive family history, start at age 40. |
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When should you start screen for colon cancer?
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Start at age 50, then every 5 years.
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When should you start pap smear for women?
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Annual pap smear at 18 yrs or at onset of sexual activity.
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List some autosomal dominant cancer syndromes.
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familial retinoblastoma
familial adenomatous polyposis multiple endocrine neoplasia syndromes. |
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List some autosomal negative cancer syndromes.
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defective DNA repair: HNPCC, xeroderma pigmentosum
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List some familial cancer syndromes.
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BRCA1
BRCA2 E-cadherin p16 or INK4a |
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Which of the following is the most common cancer predisposition syndrome?
A. Familial adenomatous polyposis B. HNPCC C. ataxia-telangiectasia D. BRCA1 |
B
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What is the pathogensis of ataxia-telangiectasia?
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Mutated ATM gene-> loss of p53-indcuced delaly in cell cycle.
Symptoms: acute sensitivity to radiation, defective lymphocyte maturation. Lead to increased lymphomas. |
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What types of carcinogens are there?
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1. chemical
2. radiation 3. viral |
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What is the difference between complete and incomplete carcinogens?
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Complete carcinogen: can induce both initiation and promotion.
Incomplete carcinogen: induce initiation only. |
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What are the two processes involved in carcinogenesis?
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1. initiation: irreversible alteration of cell's DNA.
2. promotion: reversible process of proliferation and abnormal differentiation of initiated cells after exposure to promoter. |
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Can promoter damage DNA?
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No.
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T/F: Initiation is reversible whereas prmotion is irreversible.
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F. The other way around.
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Cyclophosphamide may increase risk for _____ cancer.
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Bladder
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AZA/cyclosporin may increase risk for _____.
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lymphoma
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Which cells are most vulnerable to radiation carcinogens?
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1. hematopoietic cells
2. thyroid epithelial cells in children/adolescents 3. breast, lungs, salivary gland |
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List some microbial carcinogens.
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1. H. pylori
2. HepB, HPV, EBV: DNA 3. HTLV-1: RNA |
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Explain the pathogenesis of cervical cancer by HPV.
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E6 degrades p53
E7 associate with p21->prevents inhibition of cyclinD:CDK4. degrades RB->less cell cycle restriction. |
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Name a slow-transforming RNA oncogenic virus.
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HTLV-1: adult T cell leukemia/lymphoma. Infect CD4 cells, become latent for 40-60 years.
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Describe the mechanism of H pylori causing lymphoma and carcinoma.
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lympoma: chronic infiltrate->persistent infiltrate of B cells->mutations
carcinomas: chronic inflammation->metaplasia->dysplasia->carcinoma. |
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What is the single most environmental factor contributing to premature death in the US?
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smoking
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Surgery is curative in stage ___ tumors.
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I
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